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The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine. Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Microplastics are ubiquitous in the environment, including in the ocean, soil, and air. Therefore, there are concerns regarding human exposure. Since it is known that the surface of microplastics in various environments is chemically deteriorated by external factors such as ultraviolet rays and waves, it is essential to evaluate the biological effects of degraded microplastics. In this study, we experimented by accelerating the degradation of polyethylene (PE) using vacuum ultraviolet light and prepared PE samples with different degrees of degradation. Then, we evaluated the effects of undegraded and variously degraded PE on cells using cytotoxicity tests. Based on the cytotoxicity test results, we saw a tendency for increased cytotoxicity with increasing degradation. Therefore, this study substantially links the deterioration of microplastics with their biological effects.

Among oxygen-containing heterocyclic compounds such as coumarin and azacoumarin derivatives, the scaffold has become an important construction motif for developing new drugs. Coumarin and its derivatives possess many types of biological activities and have been reported to show significant cytotoxic activity. N-(6,8-disubstituted coumarin-3-yl)benzamides (8a-c) namely (3-N-(benzoyl) aminocoumarin-6-ylmethyl acetate (8a); N-[6-(1-acetylpyrazol-3-yldiazineyl) coumarin-3-yl] benzamide (8b); N-(8-methoxy-6-bromo-coumarin-3-yl) benzamide (8c), were synthesized via a cyclocondensation reaction of 5-(chloromethyl)-2-hydroxybenzaldehyde (3), 5-(pyrazol-3-yl-diazineyl)-2-hydroxybenzaldehyde (4), and 5-bromo-3-methoxy- 2-hydroxybenzaldehyde (5) with N-benzoylglycine (7), in good yield. Treatment of compound 8c with ammonia in the presence of anhydrous potassium carbonate to yield N-(5-bromo-8-methoxy-1-azocoumarin-3-yl) benzamide (9). Compound (9) was acetylated with acetic anhydride to give N-(2-acetoxy-5-bromo-8-methoxyquinolin-3-yl) benzamide (10). N-(substituted coumarin and azacoumarin-3-yl) benzamides (8-10) were tested for their in vitro cytotoxic activity against (HepG2) cell line. Furthermore, DNA flow cytometry investigation over HepG2 cells indicated that compound 8a demonstrated arrest at G1/S stages of the cell cycle and induction of apoptosis by rising pre-G1 stage. Compound 8a displayed a significant tubulin polymerization inhibition. KEY WORDS: Synthesis, Coumarin, Azacoumarin, Drugs, Cytotoxicity Bull. Chem. Soc. Ethiop. 2023, 37(4), 1003-1019. DOI: https://dx.doi.org/10.4314/bcse.v37i4.16

Cytotoxic CD8+T lymphocytes (CTL) eliminate infected cells or transformed tumour cells by releasing perforin-containing cytotoxic granules at the immunological synapse. The secretion of such granules depends on Ca2+-influx through store operated Ca2+channels, formed by STIM-activated Orai proteins. Whereas molecular mechanisms of the secretion machinery are well understood, much less is known about the molecular machinery that regulates the efficiency of Ca2+-dependent target cell killing. Here, we isolated total RNA from natural killer (NK) cells, non-stimulated CD8+T-cells, and from Staphylococcus aureus enterotoxin A (SEA) stimulated CD8+T-cells (SEA-CTL) and conducted whole genome expression profiling by microarray experiments. Based on differential expression analysis of the transcriptome data and analysis of master regulator genes, we identified 31 candidates which potentially regulate Ca2+-homeostasis in CTL. To investigate a putative function of these candidates in CTL cytotoxicity, we transfected either SEA-stimulated CTL (SEA-CTL) or antigen specific CD8+T-cell clones (CTL-MART-1) with siRNAs specific against the identified candidates and analyzed the killing capacity using a real-time killing assay. In addition, we complemented the analysis by studying the effect of inhibitory substances acting on the candidate proteins if available. Finally, to unmask their involvement in Ca2+dependent cytotoxicity, candidates were also analyzed under Ca2+-limiting conditions. Overall, this strategy led to the identification of KCNN4, RCAN3, CCR5 and BCL2 as potential candidates to regulate the efficiency of Ca2+-dependent target cell killing.

Sitka spruce (Picea sitchensis) needles contain a variety of bioactive compounds including phenolic compounds and flavonoids, many of which have been used in the cosmetic, pharmaceutical, and food industries. This study aimed to investigate the effects of novel extraction techniques, including ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and simultaneous ultrasound–microwave-assisted extraction (UMAE) on the recovery of phenolic, flavonoids and associated antioxidant and anti-cancer properties from Sitka spruce (Picea sitchensis) needles. The ferric reducing antioxidant power (FRAP) assay was used to evaluate the antioxidant capacity, and the Alamar Blue assay using the human brain glioblastoma cancer cell line (U-251 MG) was used to evaluate the cytotoxicity activity. Results showed that US-probe accomplished the highest recovery of phenolic and flavonoids at 38 W cm−2 for 10 min (106.3 ± 2.5 mg GAE g−1 DW and 63.2 ± 3.8 mg QE g−1 DW, respectively). Hence, the highest cytotoxicity activity of IC50 (0.0114% w/v) was achieved by US-probe at 19 W cm−2 for 10 min. However, the antioxidant capacity of (2591.3 ± 92.5 mM TE g−1 DW) was achieved under UMAE at ultrasound intensity of 38 W cm−2, microwave power of 302.4 W for 10 min. This study emphasised the potential application of UAE and MAE in the extraction of bioactive as an environmentally friendly method to be used in the valorisation of by-products in food and agro-industries. This supports the use of renewable natural resources in an efficient way to produce high-value compounds therefore it is in line with the new era of bioeconomy and its new biorefinery concepts yes

Flavan-3-ol derivatives are polyphenolic compounds with multifunctional properties. One of the flavan-3-ol derivatives, green tea catechin epigallocatechin gallate, is known to have anticancer activity as one of its multifunctional properties. We have studied the synthesis of flavan-3-ol derivatives and conducted structure-activity relationship studies; we found that the fluorinated derivatives exhibited high toxicity against HeLa and A549 cells. It was confirmed that the cytotoxicity was affected by the conformation of the flavan-3-ol skeleton and that the 2,3-cis form was dominant. The addition of fluorinated compounds increased the amount of intracellular mitochondrial superoxide, abolished the membrane potential of mitochondria, and, interestingly, formed granular aggregates containing mitochondria. When the level of LC3-II, a marker of autophagy induction, was confirmed, it suggested that the addition of the fluorinated compounds promoted autophagy. These results suggest that the novel highly cytotoxic fluorinated flavan-3-ol compound synthesized in this study promotes autophagy and induces cell death by triggering mitochondrial dysfunction. We believe that these results suggest the possibility of conferring more functionality through structural transformations of flavan-3-ol derivatives.

For a long time, ex vivo-expanded peripheral-blood-derived γδT cell (PBγδT)-based immunotherapy has been attractive, and clinical trials have been undertaken. However, the difficulty in expanding cytotoxic γδT cells to an adequate number has been a major limitation to the efficacy of treatment in most cases. We successfully re-generated γδT cells from γδT cell-derived human induced pluripotent stem cells (iPSCs). The iPSC-derived γδT cells (iγδTs) killed several cancer types in a major histocompatibility complex (MHC)-unrestricted manner. Single-cell RNA sequencing (scRNA-seq) revealed that the iγδTs were identical to a minor subset of PBγδTs. Compared with a major subset of PBγδTs, the iγδTs showed a distinctive gene expression pattern: lower CD2, CD5, and antigen-presenting genes; higher CD7, KIT, and natural killer (NK) cell markers. The iγδTs expressed granzyme B and perforin but not interferon gamma (IFNγ). Our data provide a new source for γδT cell-based immunotherapy without quantitative limitation.

The main aim of this study was to perform an integrative review on the toxic effects of resin-matrix cements and their products in contact with fibroblasts or mesenchymal cells. A bibliographic search was performed on PubMed using the following search terms: “cytotoxicity” AND “fibroblast” OR “epithelial” OR “mesenchymal” AND “polymerization” OR “degree of conversion” OR “methacrylate” OR “monomer” AND “resin cement” OR “resin-based cement”. The initial search in the available database yielded a total of 277 articles of which 21 articles were included in this review. A decrease in the viability of mouse fibroblasts ranged between 13 and 15% that was recorded for different resin-matrix cements after light curing exposure for 20 s. The viability of human fibroblasts was recorded at 83.11% after light curing for 20 s that increased up to 90.9% after light curing exposure for 40 s. Most of the studies linked the highest toxicity levels when the cells were in contact with Bis-GMA followed by UDMA, TEGDMA and HEMA. Resin-matrix cements cause a cytotoxic reaction when in contact with fibroblasts or mesenchymal cells due to the release of monomers from the polymeric matrix. The amount of monomers released from the resin matrix and their cytotoxicity depends on the polymerization parameters.

Background: Rhodanine derivatives have a proven wide range of biological activities. Objective: The aim of this study was to evaluate the cytotoxic effect of a series of rhodanine derivatives and investigate the quantitative structure-activity relationships, as well as binding modes to tyrosine kinase. Conclusion: Rhodanine derivatives could be developed as novel tyrosine kinase inhibitors in the treatment of leukemia. Methods: Cytotoxic effect on cell proliferation (CaCo-2, HeLa, MDCK-1, Hut-78, K562) in vitro was evaluated by the MTT viability assay. QSAR analysis was performed with Dragon descriptors using QSARINS software. Molecular docking was performed on the tyrosin kinase (c-Src) (PDB ID: 3G6H) using iGEMDOCK. Results: Compounds with the best inhibiting activity toward all cell lines were the ones possessing only one group in the C2 of the phenyl ring. QSAR study on the cytotoxic activity against Human T cell lymphoma achieved the model that satisfies the fitting and internal cross-validation criteria (R2 = 0.75; Q2 LOO = 0.64). Descriptors included in the model (MATS2e, MATs7e, RDF060p) revealed the importance of the presence of atoms with higher polarizability in the outer region of molecules. The findings of the molecular docking study performed on the c-Src are in accordance with the results of the QSAR study. The key interactions with binding site residues were achieved through oxygen atoms from phenoxy and rhodanine groups and rhodanine sulphur atoms.

The cytotoxicity caused by snake venoms is a serious medical problem that greatly contributes to the morbidity observed in snakebite patients. The cytotoxic components found in snake venoms belong to a variety of toxin classes and may cause cytotoxic effects by targeting a range of molecular structures, including cellular membranes, the extracellular matrix (ECM) and the cytoskeleton. Here, we present a high-throughput assay (384-well plate) that monitors ECM degradation by snake venom toxins via the application of fluorescent versions of model ECM substrates, specifically gelatin and collagen type I. Both crude venoms and fractionated toxins of a selection of medically relevant viperid and elapid species, separated via size-exclusion chromatography, were studied using the self-quenching, fluorescently labelled ECM–polymer substrates. The viperid venoms showed significantly higher proteolytic degradation when compared to elapid venoms, although the venoms with higher snake venom metalloproteinase content did not necessarily exhibit stronger substrate degradation than those with a lower one. Gelatin was generally more readily cleaved than collagen type I. In the viperid venoms, which were subjected to fractionation by SEC, two (B. jararaca and C. rhodostoma, respectively) or three (E. ocellatus) active proteases were identified. Therefore, the assay allows the study of proteolytic activity towards the ECM in vitro for crude and fractionated venoms.

Lipid-based drug delivery systems are promising systems for hydrophobic drug delivery. A lipid-based self-nano-emulsified ocular drug release system has been synthesized for improving the topical ocular delivery of hydrophobic drugs. The aim is to develop preformulation that reaches the vitreal fluid, bypassing the ocular barriers, without requiring intravitreal injection. To eliminate the complications, dexamethasone (Dex) is applied in the lipid-based system called the self-nano-emulsified drug release system (DexSNEDDS). DexSNEDDS was synthesized via different oils, surfactants, and cosurfactants suitable for ophthalmic use. The resulting system was characterized by Raman, UV, FTIR Spectra, DSC, and SEM. Dex was loaded into lipids in ratios of 31.35% Labrasol/Span 80 (1:1), 31.35% transcutol, and 17.64% oleic acid. DexSNEDDS was applied to HUVEC cells, and MTT cell viability experiments were performed to determine the cytotoxicity. The size of the prepared lipid spheres was approximately 50-200 nm according to SEM images. Zeta sizer results confirm the SEM image evaluations. Differential scanning calorimeter measurements of Dex and DexSNEDDS show characteristic peaks between 221 and 261 celcius. The fingerprint region of Dex is seen in peaks between 1700 and 1600 cm(-1) in Raman spectra and at 1740, 1640, 1350, 1070, and 887 cm(-1) in FTIR spectra, and the regions emerged in the spectra of DexSNEDDS. The viability results revealed that the difference between DexSNEDDs in treated and untreated cells was not statistically significant, and DexSNEDDS is safe for in vivo testing.

Genome-wide analysis showed that putative G-quadruplex DNA structures are prevalent in the human genome. The presence of G-quadruplex structure in the telomere and promoter region of certain oncogenes inspired people to use G-quadruplex ligand as anti-cancer agents. G-quadruplex structures, stabilized by ligand at telomere are resolved by telomerase making the cancer cells resistant to G-quadruplex ligand. So, identification of a new G-quadruplex ligand having anti-telomerase activity would be a promising strategy for cancer therapy as about 85% of human cancers are telomerase positive. A set of the drug-like compounds were screened from the ZINC database randomly and 2284 ligands were chosen following Lipinski’s rule of five that were docked with five different G-quadruplex DNA sequences in idock. We screened 43 potential G-quadruplex binders using Z-score as a normalization scoring function. The compound (ZINC ID-05220992) gave the best score (average idock = −10.17 kcal/mol, average normalized idock = −3.42). We performed G4 FID assay, CD analysis to understand its binding with three different G-quadruplex DNA sequences, and checked its anti-telomerase activity in A549 cells using TRAP assay. We observed that this compound had an intrinsic fluorescence, capability to stain live cells with a blue fluorescence, and a specific affinity to only 22AG out of three different G-quadruplex DNA sequences under study. It showed cytotoxicity, good permeability to live cells, and a significant reduction of telomerase activity in human A549 cells at a very low dose. So, this compound has strong potential to be an anti-cancer drug.Graphical AbstractHighlightsA set of compounds were screened randomly by a High throughput method and Lipinski’s rule of five from ZINC database to identify potential G4-binders.The compound (ZINC ID-05220992) was screened after docking with five G-quadruplex DNAIt binds G-quadruplex DNA 22AG as detected by TO displacement and CD spectroscopy.It inhibits telomerase activity in A549 cells and also cytotoxic to this cell.It penetrates live A549 cell in culture and stains it with blue fluorescence

Globally, rotavirus (RV) is the most common cause of acute gastroenteritis in infants and toddlers; however, there are currently no agents available that are tailored to treat rotavirus infection in particular. Improved and widespread immunization programs are being implemented worldwide to reduce rotavirus morbidity and mortality. Despite certain immunizations, there are no licensed antivirals that can attack rotavirus in hosts. Benzoquinazolines, chemical components synthesized in our laboratory, were developed as antiviral agents, and showed good activity against herpes simplex, coxsackievirus B4 and hepatitis A and C. In this research project, an in vitro investigation of the effectiveness of benzoquinazoline derivatives 1–16 against human rotavirus Wa strains was carried out. All compounds exhibited antiviral activity, however compounds 1–3, 9 and 16 showed the greatest activity (reduction percentages ranged from 50 to 66%). In-silico molecular docking of highly active compounds, which were selected after studying the biological activity of all investigated of benzo[g]quinazolines compounds, was implemented into the protein’s putative binding site to establish an optimal orientation for binding. As a result, compounds 1, 3, 9, and 16 are promising anti-rotavirus Wa strains that lead with Outer Capsid protein VP4 inhibition.

The aim was to evaluate in vitro cytotoxicity and genotoxicity of Bio-C Repair (BCR), compared to Endosequence BC Root Repair (ERRM), MTA Angelus (MTA-Ang), and MTA Repair HP (MTA-HP). MC3T3 osteoblastic cells were exposed to extracts of the repairing bioceramic cements. After 1, 3, and 7 days, cytotoxicity and genotoxicity were evaluated by MTT and Micronucleus tests, respectively. Cells not exposed to biomaterials were used as a negative control. Data were compared using ANOVA two-way, followed by the Tukey Test (α=5%). MTA-Ang and MTA-HP showed no difference in relation to control regarding cytotoxicity in any experimental times. BCR and ERRM reduced cell viability after 3 and 7 days (p

Background: Increasing rates of acquired resistance have justified the critical need for novel antimicrobial drugs. One viable concept is the modification of known drugs. Methods & results: 21 mafenide-based compounds were prepared via condensation reactions and screened for antimicrobial efficacy, which demonstrated promising activity against both Gram-positive and Gram-negative pathogens, pathogenic fungi and mycobacterial strains (minimum inhibitory concentrations from 3.91 μM). Importantly, they retained activity against a panel of superbugs (methicillin- and vancomycin-resistant staphylococci, enterococci, multidrug-resistant Mycobacterium tuberculosis) without any cross-resistance. Unlike mafenide, most of its imines were bactericidal. Toxicity to HepG2 cells was also investigated. Conclusion: Schiff bases were significantly more active than the parent drug, with iodinated salicylidene and 5-nitrofuran/thiophene-methylidene scaffolds being preferred in identifying the most promising drug candidates.

Teucrium species have been among the most commonly used traditional medicinal plants and they are known to have extensive therapeutic applications. The main focus of this study, Teucrium multicaule is also renowned for being an important medicinal and aromatic plant in Turkiye. Volatile profiling of the essential oils was conducted by GC MS, phytochemical profiling of the ethanol extracts was carried out by LC HRMS, antioxidant, anticholinesterase, antityrosinase, antiurease, antidiabetic, anticancer, and antimicrobial activities were revealed by different assays. Germacrene D was the most abundant compound in the essential oils from Diyarbakir (TmuD) with 45.4%, and Batman (TmuB) with 54.7%. All extracts were found to be quite rich in phytochemicals by LC HRMS, and herniarin, caffeic acid, naringenin, luteolin, scutellarein, hispidulin, rhamnocitrin, penduletin, eupatilin, (-)-epigallocatechin gallate, hederagenin, and verbascoside were found to be present in all extracts. T. multicaule roots extract from Diyarbakir (TmuRD) demonstrated the highest radical scavenging, a-amylase inhibitory (59.82§0.36%), and antibutyrylcholinesterase activity (61.96§ 1.72%), whereas T. multicaule aerial parts extract from Batman (TmuHB) exhibited the strongest antityrosinase (66.17§0.92%), antiurease (67.85§0.69%), and cytotoxic (54.76 § 1.57 mg/mL) activities. TmuRD also showed significant antimicrobial activity against S. epidermidis with 156.2 mg/mL MIC value. As revealed by this first detailed report on T. multicaule, the plant demonstrates various important biological activities attributed to its rich phytochemicals, which also justifies its use in ethnomedicine.

The use of fungal pigments as dyes is attractive for various industries. Fungal pigments arise a strong interest because they are suitable for large-scale industrial production and have none of the drawbacks of synthetic pigments. Their advantages over synthetic or vegetal dyes mark them as a prime target. Azaphilones are fungal polyketides pigments bearing a highly oxygenated pyranoquinone bicyclic core produced by numerous species of ascomyceteous and basidiomyceteous fungi. In order to find new azaphilones dyes, the fungal strain Penicillium hirayamae U., a known producer of azaphilone but, chemically, barely studied so far, was investigated by molecular networking and led to the isolation of three new azaphilones, penazaphilone J-L, along with the known penazaphilone D, isochromophilone VI, and sclerketide E. Their structures were determined based on extensive NMR and the absolute configurations by ECD. All compounds were evaluated for their cytotoxic activity against human cell lines and human pathogenic-resistant strains.

Under healthy conditions, pro- and anti-phagocytic signals are balanced. Cluster of Differentiation 47 (CD47) is believed to act as an anti-phagocytic marker that is highly expressed on multiple types of human cancer cells including acute myeloid leukemia (AML) and lung and liver carcinomas, allowing them to escape phagocytosis by macrophages. Downregulating CD47 on cancer cells discloses calreticulin (CRT) to macrophages and recovers their phagocytic activity. Herein, we postulate that using a modified graphene oxide (GO) carrier to deliver small interfering RNA (siRNA) CD47 (CD47_siRNA) in AML, A549 lung, and HepG2 liver cancer cells in co-culture in vitro will silence CD47 and flag cancer cells for CRT-mediated phagocytosis. Results showed a high knockdown efficiency of CD47 and a significant increase in CRT levels simultaneously by using GO formulation as carriers in all used cancer cell lines. The presence of CRT on cancer cells was significantly higher than levels before knockdown of CD47 and was required to achieve phagocytosis in co-culture with human macrophages. Lipid nanoparticles (LNPs) and modified boron nitride nanotubes (BNPs) were used to carry CD47_siRNA, and the knockdown efficiency values of CD47 were compared in three cancer cells in co-culture, with an achieved knockdown efficiency of >95% using LNPs as carriers. Interestingly, the high efficiency of CD47 knockdown was obtained by using the LNPs and BNP carriers; however, an increase in CRT levels on cancer cells was not required for phagocytosis to happen in co-culture with human macrophages, indicating other pathways’ involvement in the phagocytosis process. These findings highlight the roles of 2D (graphene oxide), 1D (boron nitride nanotube), and “0D” (lipid nanoparticle) carriers for the delivery of siRNA to eliminate cancer cells in co-culture, likely through different phagocytosis pathways in multiple types of human cancer cells. Moreover, these results provide an explanation of immune therapies that target CD47 and the potential use of these carriers in screening drugs for such therapies in vitro.

Nanomedicine has emerged as an area of research that has earned a lot of attention in the past decade along with frequent and sustained advancements leading to its extensive plethora of biomedical applications. Following the same, the drug carrier systems like gold nanoparticles (AuNPs) have become the success stories with many marketed formulations now and has proved to be a most suitable answer to the drug delivery concers due to their exclusive electrical and optical properties. They serve as one of the best surfaces to either adsorb, attach, or conjugate and exhibit remarkable optoelectronic, physicochemical, morphological and functional properties. In this study, Gabapentin (GBP) a known FDA approved anti-epileptic drug is selected for improving its pharmaceutical limitations and we have synthesized monodispersed AuNPs for GBP conjugation using citrate reduction method. Here the research group has modified AuNP surfaces with three different thiol moieties namely, Mercaptopropionic acid (3-MPA), 11-Mercaptoundecanoic acid (11-MUA) and the amino acid L-Cysteine (L-Cys) and then attached the GBP with these linkers. The synthesized GBP–AuNP nano-conjugate moieties were further characterized and tested for their in-vitro cytotoxicity, release kinetics and stability properties. The in-vitro release kinetics and cytotoxicity (MTT-Assay) analysis of the formulated GBP–AuNP nano-conjugates along with all the 3 types of linkers was carried out and after the data analysis for the same, it was observed that the GBP–AuNP nano-conjugate with L-Cys linker exhibited the sustained release pattern and non- significant cytotoxicity followed by MUA and MPA, respectively. Moreover, the assessment of GBP-AuNPs evaluated through the comprehensive release kinetics analysis, reinforced the GBP-thiol linkers as potentially more effective and competent than GBP alone. Furthermore, all the experimental data was validated by statistical method, and it can be concluded from the present study that the symmetrical monodispersed AuNPs formulation coated with stable functionalized thiol layer were synthesized with minimal cytotoxicity and can be further explored as an efficient drug delivery system for therapeutic application.

Three common Apolipoprotein E isoforms, ApoE2, ApoE3, and ApoE4, are key regulators of lipid homeostasis, among other functions. Apolipoprotein E can interact with amyloid proteins. The isoforms differ by one or two residues at positions 112 and 158, and possess distinct structural conformations and functions, leading to isoform-specific roles in amyloid-based neurodegenerative diseases. Over 30 different amyloid proteins have been found to share similar characteristics of structure and toxicity, suggesting a common interactome. The molecular and genetic interactions of ApoE with amyloid proteins have been extensively studied in neurodegenerative diseases, but have not yet been well connected and clarified. Here we summarize essential features of the interactions between ApoE and different amyloid proteins, identify gaps in the understanding of the interactome and propose the general interaction mechanism between ApoE isoforms and amyloid proteins. Perhaps more importantly, this review outlines what we can learn from the interactome of ApoE and amyloid proteins; that is the need to see both ApoE and amyloid proteins as a basis to understand neurodegenerative diseases.

In the treatment of acute lymphoblastic leukemia, 6-mercaptopurine (6-MP) is commonly used. Yet, short half-life in plasma, poor water solubility, severe side effects and variable bioavailability limit its use. GSH-responsive prodrugs (3&5) and biotin receptor targeted were made to enhance the intracellular accumulation related to 6-MP in the cancer cell. In compound 5, nanoparticles (NPs) have been prepared through conjugating 6-MP to carbon dots (nanocarriers) through GSH-sensitive carbonyl vinyl sulfide linkage, and surface decoration with biotin. Compound 3 was synthesized by direct conjugation of 6-MP to the biotin through GSH-sensitive linkage. In-vitro drug release study of NPs showed good stability in the phosphate buffer saline (PBS), which contains 100 µM GSH at (pH 7.40). Yet, the cumulative rate of the drug release that is associated with samples that contain the GSH medium of 10 mM reached 79.6% in acetate buffer at (pH 5.8). In vitro cytotoxicity study (MTT assay) demonstrated that compound 3 showed higher inhibition ratios on biotin receptor overexpressed cell lines (MCF-7, HepG2) and lower cytotoxicity on normal cell lines (CHO). Compound 5 showed good activity, comparable to 6-MP against (MCF-7, HepG2), and much lower cytotoxicity on (CHO).

In the last 20 years, the development of stimuli-responsive drug delivery systems (DDS) has received great attention. Hydrogel microparticles represent one of the candidates with the most potential. However, if the role of the cross-linking method, polymer composition, and concentration on their performance as DDS has been well-studied, still, a lot needs to be explained regarding the effect caused by the morphology. To investigate this, herein, we report the fabrication of PEGDA–ALMA-based microgels with spherical and asymmetric shapes for 5-fluorouracil (5-FU) on-demand loading and in vitro pH-triggered release. Due to anisotropic properties, the asymmetric particles showed an increased drug adsorption and higher pH responsiveness, which in turn led to a higher desorption efficacy at the target pH environment, making them an ideal candidate for oral administration of 5-FU in colorectal cancer. The cytotoxicity of empty spherical microgels was higher than the cytotoxicity of empty asymmetric microgels, suggesting that the gel network’s mechanical proprieties of anisotropic particles were a better three-dimensional environment for the vital functions of cells. Upon treatment with drug-loaded microgels, the HeLa cells’ viability was lower after incubation with asymmetric particles, confirming a minor release of 5-FU from spherical particles.

In recent years, researchers have shown an increased interest in using medicinal plants for the synthesis of silver nanoparticles (AgNPs) having various therapeutic properties. Centella asiatica (CA), a medicinal plant, has been used to treat minor burn wounds, psoriasis, and hypertrophic wounds among many other pathological conditions. The current study aimed to synthesize CA coated AgNPs (CA-AgNPs) with appropriate biocompatibility and various therapeutic properties, including antimicrobial and analgesic activities. The synthesized CA-AgNPs were characterized by ultraviolet-visible (UV-Vis) spectroscopy, zeta potential measurements, and fourier transform infrared (FT-IR) spectroscopy. The formation of spherical CA-AgNPs was confirmed by a single surface plasmon resonance (SPR) peak emerging at 420 nm wavelength by UV-Vis. The average hydrodynamic diameter and zeta potential of the particles were found to be 29.5 nm and -24.5 mV, respectively. The FT-IR analyses showed that the AgNPs were coated and stabilized by bioactive compounds from the CA extract. MTT cytotoxicity assay revealed that CA-AgNPs at ≤1 mM concentrations exhibited biocompatibility for L929 fibroblast cells. The antimicrobial activity of CA-AgNPs was confirmed by significant inhibition of Staphylococcus aureus and Escherichia coli. In addition, the analgesic effect of CA-AgNPs was investigated for the first time in the literature by tail-flick and hot plate methods, and statistically significant results were obtained for both methods. Taken together, these results suggest that CA-AgNPs can be used as an effective antibacterial and analgesic agent in a variety of biomedical applications, including coating wound dressings.

Burada, steroidal olmayan anti-enflamatuar ilaç niflumik asit ve 3-pikolin içeren yeni bir gümüş(I) kompleksi sentezlendi ve FT-IR, 1H NMR, elemental ve termik analiz teknikleri ile karakterize edildi. Bu teknikler, sentezlenen kompleksin formülünün [Ag(nif)(3-pic)] olduğunu gösterdi. Kompleks, ligand (niflumik asit) ve gümüş iyonlarının tek başına sitotoksik yeteneği, insan meme adenokarsinomu (MDA-MB-453), akciğer adenokarsinomu (A-549), kolorektal adenokarsinom (HT-29) ve fare fibroblast hücre hatlarına (3T3-L1) karşı test edildi. XTT sonuçları, AgNO3 ve niflumik asidin tek başına kanser ve sağlıklı hücre hatları üzerinde orta düzeyde sitotoksisite sergilemesine rağmen, kompleksin kanser hücreleri üzerinde doza bağlı bir şekilde güçlü sitotoksik aktivite gösterdiğini gösterdi. Kompleksin en güçlü sitotoksisitesi ve en yüksek seçiciliği HT-29 hücrelerinde belirlendi. Bu bulgular, gelişmiş antikanser çalışmalarında yeni gümüş(I) kompleksinin değerlendirilmesi için temel çıktılar sağlar.

Background and Aims: It is thought that thymoquinone might have a crucial role in preventing DNA damage, regulating DNA repair mechanisms, and inhibiting the formation of a cancer. Studies on the cytotoxic and genotoxic effects of thymoquinone together with etoposide in cervical carcinoma cells (HeLa) are not adequate. The objective of this study is to evaluate the ef- fect of combinations with thymoquinone on etoposide cytotoxicity and genotoxicity in HeLa cells. Methods: Cytotoxicity was evaluated by MTT assay and genotoxicity was determined by Comet assay. Results: The IC50 values of thymoquinone were 233.6 μM and 145.5 μM, and the IC50 values of etoposide were 167.3 μM and 52.7 μM for 24 and 48 h, respectively. Thymoquinone significantly decreased the approximate IC50 value of etoposide in doses of 15.63 μM and above for 24 h and 31.5 μM and above for 48 h in a dose-dependent manner. 0.1-5 μM thymoquinone and 1 μM etoposide alone did not cause DNA damage, but at higher doses increased DNA damage significantly in a dose-dependent manner. Thymo- quinone significantly reduced DNA damage induced by 10 μM etoposide at the doses of 0.1-10 μM. Conclusion: Our results show that thymoquinone might increase the cytotoxic and genotoxic effects of etoposide in HeLa cells at high doses and reduce DNA damage at low doses that are not cytotoxic, which suggests that etoposide may increase its anticancer effect at high doses, but comprehensive studies are needed on this subject. This study is a preliminary study and will contribute to the development of new treatment strategies.

Benzoylacetone (1) underwent a series of multi-component reactions with aromatic aldehydes and malononitrile or ethyl cyanoacetate to produce the pyran derivatives 4a-f. The latter compounds reacted with malononitrile or ethyl cyanoacetate to yield the condensation products 5a-m. On the other hand, the reaction of 4a-f with either the diazonium salts 6a-c yielded the arylhydrazone derivatives 7a-i. The multi-component reaction of (1) with aromatic adehydes and cyclohexan-1,3-dione produced the pyran derivatives 9a-c. Compound 1 underwent the Gewald’s reactions with elemental sulfur and malononitrile or ethyl cyanacetate yielding the thiophene derivatives 10a,b. Evaluations of the synthesized products were carried out against some selected cancer cell lines and the most active compounds were further evaluated against the seventeen cancer cell lines classified according to the disease. Morphological changes of A549 cell line by the effect of compound 7k was studied using microenvironment of the lung tissue where an excellent results was obtained. KEY WORDS: Benzoylacetone, Multi-component reactions, Pyran, Thiophene, Arylhydrazone, Cytotoxicity Bull. Chem. Soc. Ethiop. 2023, 37(2), 405-425. DOI: https://dx.doi.org/10.4314/bcse.v37i2.12

Ti(III) and (IV) hydrazide complexes were synthesized, characterized, and screened for their tyrosinase and lipoxygenase inhibitory and cytotoxic activities. The geometry of Ti(III) hydrazide complexes is tentatively assigned as octahedral. Magnetic moments were found around 1.7 B.M. and electronic spectral transition in the range of 495-518 nm. Evaluation of Ti(IV) and Ti(III) hydrazide complexes for tyrosinase and lipoxygenase inhibitory activities revealed varying inhibition potential. Hydrazide ligands were inactive against tyrosinase, while significant activity was observed against lipoxygenase (LOX). Good to moderate inhibition activity was observed by Ti(IV) and Ti(III) hydrazide complexes against both enzymes. At the same time, promising results were obtained for Ti(IV) hydrazide complexes against tyrosinase enzymes suggesting their broad application as tyrosinase inhibitors. Complex 4d possess negative inhibition, thus behaving as a tyrosinase activator. The docking results showed a good correlation between complex experimental activities and binding energies. Cytotoxic investigation revealed the non-toxicity of complexes against normal cells. KEY WORDS: Titanium(III) and titanium(IV) hydrazide complex, Tyrosinase, Lipoxygenase, Inhibition, Molecular docking, Cytotoxicity Bull. Chem. Soc. Ethiop. 2023, 37(2), 315-333. DOI: https://dx.doi.org/10.4314/bcse.v37i2.6

A series of new thiophene derivatives was prepared through nucleophilic substitution reactions of the precursor N-(4-substituted-phenyl)-5-(2-chloroacetamido)-4-cyano-3-methylthiophene-2-‎carboxamides 4a and 4b with different sulfur and/or nitrogen nucleophilic reagents (namely; mercaptoacetic acid, 2-mercaptobenzothiazole, 5-(phenylamino)-1,3,4-thiadiazole-2-thiol, 2-mercapto-4,6-dimethylnicotinonitrile, 3-arylazo-4-mercapto-4-(phenylamino)-but-3-en-one derivatives, ammonium thiocyanate, piperidine and/or morpholine). The structures of the prepared thiophene compounds were characterized by spectral analysis. Their cytotoxicity was evaluated against two human cancer cell lines (HepG2 and MCF-7) and indicated promising results. Pretreatment of HepG2 cells with the tested compound 4b sensitized the cells to the cytotoxicity of sorafenib, leading to a significant decrease in the IC50 from 3.9 to 0.5 µM. KEY WORDS: N-(Thienyl)-2-chloroacetamide, Bis-thiophene, Thieno[2,3-d]pyrimidine, Ammonium thiocyanate, Cytotoxicity Bull. Chem. Soc. Ethiop. 2023, 37(2), 373-389. DOI: https://dx.doi.org/10.4314/bcse.v37i2.10

Nanosized silicate-substituted hydroxyapatites, characterized by the general formula Ca9.8−x−nSrnZnx(PO4)6−y(SiO4)y(OH)2 (where: n = 0.2 [mol%]; x = 0.5–3.5 [mol%]; y = 4–5 [mol%]), co-doped with Zn2+ and Sr2+ ions, were synthesized with the help of a microwave-assisted hydrothermal technique. The structural properties were determined using XRD (X-ray powder diffraction) and Fourier-transformed infrared spectroscopy (FT-IR). The morphology, size and shape of biomaterials were detected using scanning electron microscopy techniques (SEM). The reference strains of Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa were used to assess bacterial survivability and the impact on biofilm formation in the presence of nanosilicate-substituted strontium-hydroxyapatites. Safety evaluation was also performed using the standard cytotoxicity test (MTT) and hemolysis assay. Moreover, the mutagenic potential of the materials was assessed (Ames test). The obtained results suggest the dose-dependent antibacterial activity of nanomaterials, especially observed for samples doped with 3.5 mol% Zn2+ ions. Moreover, the modification with five SiO4 groups enhanced the antibacterial effect; however, a rise in the toxicity was observed as well. No harmful activity was detected in the hemolysis assay as well as in the mutagenic assay (Ames test).

Designed Chalcone-Dihydropyrimidinone hybrid compounds were synthesized expeditiously. The hybridization was performed through the Copper-catalyzed Alkyne-Azide Cycloaddition (CuAAC) from the propargyloxy chalcones and azido-dihydropyrimidinones. The hybrid products were prepared in five steps with a 30–48% overall yield. Most of the compounds showed selective cytotoxicity and lower IC50 values (

Ginger (Zingiber officinale Rosc.) is well known as distinctive spice with considered therapeutic values. In the current work we aimed to investigate cytotoxic effect, phytochemical screening and genetic analysis of ginger callus and their rhizome. Cytotoxicity of ginger rhizome and callus extracts was examined against some human cancer cell lines HT29, HT116 and MCF-7 by MTT method. Phytochemicals were screened by thin layer chromatography (TLC) and genetic analysis was performed by ISSR markers. Ginger rhizome principle components, 6-gingerol and 6-shogoal were used as standards to detect their presence in callus. Results showed that, rhizome extracts displayed a strong cytotoxicity towards all tested cancer cells with the highest activity (IC50 20.4 ± 3.0 µg/mL; P 100 µg/mL in all examined cancer cell lines. TLC chromatograms of rhizome and callus extracts revealed the presence of phenols and terpenes, whereas 6-gingerol and 6-shogaol were only detected in rhizome extracts. Genetic analysis by ISSR markers revealed occurrence some genetic changes in DNA of callus compared to that of rhizome with total polymorphism 23.07%. In conclusion, ginger cytotoxicity to HT29, HT116 and MCF-7 cancer cells was mainly associated with the presence of 6-shogaol and 6-gingerol in extracts, which appeared as strong cytotoxic effect in rhizome compared to non-cytotoxic effect was evaluated in the callus extracts. Therefore, further studies on the callus elicitation and precursors feeding to induce biosynthesis of ginger bioactive molecules are recommended.

Background: Phytochemicals are used to treat lung cancer in contemporary and traditional medicine. The limitations of known chemotherapeutic drugs such as non-specificity, resistance, and toxicity restrict their use for lung cancer treatment. Therefore, the search for target-specific novel entities is required continuously. Objective: Linalool, a monoterpene alcohol that possesses antiviral, anti-inflammatory, and antibacterial properties, is present in sweet basil, laurel, jasmine, rosewood, and lavender. Previous reports revealed its anticancer potential against colon, breast, and liver cancer. In this study, linalool's efficacy in targeting biomarkers associated with different lung cancer stages has been investigated Methods: The in silico molecular docking analysis was used to explore drug-receptor interaction, and further, linalools cytotoxicity potential was evaluated on lung adenocarcinoma cell line (A549). The toxicity profiling of linalool was done by ADMET analysis. Results: In the results, Linalool revealed an excellent binding affinity with the selected targets. It showed the highest interaction with BRAF with the binding energy of -5.6 kcal/mol. Furthermore, it successfully interacts within the binding pocket of BRAF, similar to its inhibitor (Sorafenib). In MTT analysis, linalool significantly reduces the percent viability IC30 474.94 ± 43.12, 379.33 ± 49.5, and 183.77 ± 66.7 μM in A549 cell lines for 24, 48, and 72 h, respectively. Conclusion: These results concluded that linalool possesses chemopreventive potential against lung cancer by interacting or modulating selected biomarkers associated with a lung cancer diagnosis, progression, and proliferation.

Halophilic organisms are a novel attractive option as cell factories for the production of industrially valuable bioproducts. Halomonas elongata is the cell factory of choice for ectoine production, but its levan production has not been well researched. Based on this scientifc motivation, in this study, we evaluated the chemical and biological properties of levan produced by the halophilic extremophile Halomonas elongata 153B (HeL). First, the central composite design was used to determine the optimal process variables for maximum levan biosynthesis. Then, the levan produced from HeL was purifed, quantifed, and chemically characterized with FTIR, 1 H-NMR, and GPC analyses. This was followed by antioxidant, anti-infammatory, antibioflm, and antimicrobial activity tests to assess its biological activities as well as a cytotoxcity assay. Maximum levan yields of 5.13±0.38 g/L were achieved after dialysis at the optimum levels of process variables. The 1 H-NMR spectrum of HeL revealed characteristic signals. It showed a strong antioxidant activity of 67.88% and the best radical scavenger. At a concentration of 400 µg/mL, HeL showed the most anti-infammatory efcacy. Also, at all indicated concentrations (250, 500, 750, and 1000 μg/mL) HeL, acted against bioflms formed by Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC 11778, Candida albicans ATCC 10231. Furthermore, HeL displayed antimicrobial activities against all strains tested. Finally, HeL showed high Cell viability in all dosages and no cytotoxicity was observed. In light of these results, HeL may have high potential in the medical, pharmaceutical and dermo-cosmetics industries.

The aim of this study was to analyse the cytocompatibility of Surefil One (SuO) with respect to the release of monomers from the material. The following reference materials were chosen: SDR Flow Plus (SDR, Dentsply Sirona, Konstanz, Germany), One Q Bond (Q, Dentalica, Milan, Italy), and Ketac (K, 3M-ESPE, USA). Fifteen dentin discs (2 mm thickness and diameter) were obtained from 15 third molars and were used in this study. After dentin disc permeability measurement, murine fibroblasts were grown, and the pulp surface of the dentinal disc was placed in direct contact with the cells immersed in DMEM. The experimental materials were positioned on the occlusal side of each dentinal disc until a uniform thickness of 2 mm was obtained. Then, the discs were inserted into an artificial pulp chamber for 24 hours to assess the cytocompatibility. Afterwards, the moles of monomers leached from the specimens in DMEM were determined using HPLC. Statistical analysis was performed using ANOVA ( p < 0.05 ). Under the experimental conditions, the toxic effect induced by all tested materials was slight or absent. Diurethane dimethacrylate and acrylic acid were not found in the culture media. It is concluded that all materials have good cytocompatibility consistent with the nondeterminability of the monomers released after polymerization.

The modulatory effect of C-Vx, a novel therapeutic agent, on the immune system of COVID-19 patients was investigated. The functions of T and NK cells of COVID-19 patients with different disease severity were evaluated by flow cytometry in response to C-Vx stimulation. The levels of pro- and anti-inflammatory cytokines were detected by multiplex assay in supernatants after cell culture with C-Vx. Bradykinin, IRF3, and IFN-alpha levels were also measured by ELISA in the presence or absence of C-Vx stimulation. As a result, increased CD107a expression was observed on NK cells in response to C-Vx addition. The proliferation of T cell subsets was increased by C-Vx, decreasing by disease severity. IL-4 and IL-10 levels were elevated while IFN-gamma and IL-17 levels were reduced in T cells following C-Vx stimulation. However, the levels of pro-inflammatory IL-1 beta, IL-6, IL-8, IFN-gamma and GM-CSF were significantly increased upon C-Vx stimulation. IFN-alpha levels tended to increase after incubation with C-Vx. These findings support an immunomodulatory action of C-Vx on the immune system of patients with a mild and moderate phase of COVID-19.

Abstract: New ruthenium complexes bearing bipyridine ligands with different substituents (propyl, hexyl, isobutyl, and benzyl) were synthesized and characterized by MS, NMR, FTIR, and UV/Visible spectroscopy. Moreover, their cytotoxic, anti-carcinogenic, and anti-biofilm activities were evaluated. The electrochemical properties of the complexes have been investigated by cyclic voltammetry. The HOMO and LUMO energy levels of RuL1-RuL4 were found to be (-5.45 eV)-(-5.46 eV) and (-2.98 eV)-(-3.01 eV), respectively. Cytotoxic activities of ruthenium complexes were investigated in Caco-2, HepG2, and HEK293 cells. It was found that RuL3 showed a cytotoxic effect on cancer cells without affecting non-cancerous cells at applied doses. The presence of the benzyl group may increase the cytotoxic effect of RuL3 compared to other derivatives that contain the alkyl group. The apoptotic effect of the RuL3 derivative was determined by using Arthur image-based cytometer. It found that RuL3 induced apoptosis in Caco-2 (5-fold) and HepG2 (2-fold) cancer cells, respectively. All ruthenium complexes inhibited Staphylococcus aureus ATCC 29213 biofilm, but RuL3 had a more pronounced effect. Moreover, RuL3 had biofilm inhibition and biofilm degradation effect, while RuL1 and RuL4 demonstrated only biofilm inhibition. The fluorescent microscopy analysis confirmed the antibiofilm effect of ruthenium complexes. All of these results clearly showed that RuL3 showed cytotoxic and apoptotic effects on cancer cells.

The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha -particle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors., Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) [E-26/200.815/2021, E-26/010.000981/2019, E-26/010.002362/2019, E-26/211.269/2021, E-26//211.207/2021, E-26/202.320/2021]; CNPq [301069/2018-2]; National Nuclear Energy Commission [01341.011064/2021-71], This study was funded by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ) (Cientista do Nosso Estado: E-26/200.815/2021; Rede NanoSaude: E-26/010.000981/2019, Pesquisa na UEZO: E-26/010.002362/2019; Tematicos: E-26/211.269/2021, Infraestrutura e Pesquisa na UEZO e UERJ: E-26//211.207/2021, Bolsa de Pos Doutorado Senior (PDS): E-26/202.320/2021) CNPq (Bolsa de Produtividade 1B: 301069/2018-2) to Ralph Santos-Oliveira. National Nuclear Energy Commission (Bolsa de Posdoutorado CNEN: 01341.011064/2021-71) to Martha Sahyli Ortega Pijeira.

Herbs are widely used in the treatment of diseases as colds, infections, and cancer. In this work, we evaluate Alcea calvertii, which is a perennial herbaceous plant belonging to the Malvaceae family. It spreads in Anatolia and Mediterranean region and has important uses in terms of ethnobotany. In this study, it was aimed to evaluate the cytotoxic potentials and to investigate the antioxidant activities of methanol, water, chloroform, and ethyl acetate extracts of the aerial parts of Alcea calvertii. For that, the antioxidant activity of Alcea calvertii was determined by four different methods [total phenolic content (TPC), ferric reducing antioxidant power (FRAP), copper reducing antioxidant capacity (CUPRAC) and 2,2-diphenylpicrylhydrazil (DPPH) radical scavenging activity. The cytotoxicity potential of extracts was assessed in the human lung cancer cell line (A549) by MTT assay. It was observed that the highest antioxidant activity was in the methanol extract and the antioxidant activity increased with increasing extract concentration; The TPC values were between 62.5 - 414.6 GAE µg mL-1, the FRAP values were between 115.7 - 1321.4 µM Trolox equivalent g-1, CUPRAC values were between 177.1 - 1321.4 µM Trolox equivalent g-1, and IC50 values in DPPH determination were between 0.0089 - 3.5370 mg mL-1. The extracts caused cytotoxicity in a concentration dependent manner, the IC50 values were calculated to be between 36.8 - 62.64 µg mL-1. It is concluded that Alcea calvertii could be an important herb in developing new drugs., Bitkiler ve bitkisel ilaçlar soğuk algınlığı, enfeksiyonlar ve kanser gibi farklı hastalıkların tedavisinde kullanılmaktadır. Alcea calvertii, Malvaceae familyasına ait çok yıllık otsu bir bitkidir. Anadolu ve Akdeniz bölgesinde yayılan bu bitki etnobotanik açısından önemli bir yere sahiptir. Bu çalışmada, Alcea calvertii bitkisinin topraküstü kısımlarının metanol, su, kloroform ve etil asetat ekstrelerinin antioksidan aktiviteleri ile bu ekstrelerin sitotoksik potansiyellerinin incelenmesi amaçlanmıştır. Bu kapsamda, Alcea calvertii’nin antioksidan aktivitesi dört farklı yöntem [toplam fenolik içeriği (TPC), ferrik indirgeyici antioksidan gücü (FRAP), bakır indirgeyici antioksidan kapasitesi (CUPRAC) ve 2,2-difenilpikrilhidrazil (DPPH) radikal süpürme aktivitesini] ile tespit edilmiştir. İnsan akciğer kanseri hücre hattındaki (A549) sitotoksik potansiyeli ise MTT testi ile belirlenmiştir. En yüksek antioksidan aktivitenin metanol ekstresinde olduğu ve artan ekstre konsantrasyonu ile antioksidan aktivitenin arttığı gözlenmiştir; TPC değerlerinin 62,5- 414,6 GAE µg mL-1, FRAP değerlerinin 115,7- 1321,4 µM Trolox eşdeğeri g-1, CUPRAC değerlerinin 177,1 - 1321,4 µM Trolox eşdeğeri g-1, DPPH tespitinde IC50 değerlerinin 0,0089- 3,5370 mg mL-1 arasında hesaplanmıştır. Ekstreler konsantrasyona bağlı olarak hücre ölümüne neden olmuştur ve IC50 değerleri 36,8-62,64 µg mL-1 arasında bulunmuştur. Bu sonuçlar umut verici olup daha kapsamlı çalışmalar ile incelenmesinin önemli olduğu düşünülmektedir.

This work aimed to investigate, for the first time, the chemical composition and cytotoxicity of Dillenia reticulata King’s essential oil. The essential oil was obtained through hydrodistillation, and its volatile components were analyzed through gas chromatography (GC-FID) and gas chromatography-mass spectrometry (GC-MS) techniques. Twelve components, which constitutes more than 99.49% of oil content, were successfully identified. The most prominent components were bicyclogermacrene (44.18%), germacrene D (14.49%), β-gurjunene (12.59%), and elemol (12.25%). The cytotoxicity of essential oil was evaluated using an MTT assay. The essential oil exhibited cytotoxicity against three cancer cell lines which are HepG2, MCF7 and A549 with the IC50 values ranging from 61.5-68.5 μg/mL. The present study highlights the potential of using essential oil as an alternative for the development of chemopreventive or cosmetic agents for the pharmaceutical industry. KEY WORDS: Dillenia reticulata, Dilleniaceae, Essential oil, Cytotoxicity, Bicyclogermacrene Bull. Chem. Soc. Ethiop. 2023, 37(1), 245-249. DOI: https://dx.doi.org/10.4314/bcse.v37i1.19 &nbsp

Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria tenuissima AUMC14342 ethyl acetate extract on HeLa (cervical cancer), SKOV-3 (ovarian cancer), and MCF-7 (breast adenocarcinoma) cell lines. The extract showed potent effect on MCF-7 cells with an IC50 value of 55.53 μg/mL. Cell cycle distribution analysis of treated MCF-7 cells revealed a cell cycle arrest at the S phase with a significant increase in the cell population (25.53%). When compared to control cells, no significant signs of necrotic or apoptotic cell death were observed. LC-MS/MS analysis of Alternaria tenuissima extract afforded the identification of 20 secondary metabolites, including 7-dehydrobrefeldin A, which exhibited the highest interaction score (−8.0156 kcal/mol) in molecular docking analysis against human aromatase. Regarding ADME pharmacokinetics and drug-likeness properties, 7-dehydrobrefeldin A, 4’-epialtenuene, and atransfusarin had good GIT absorption and water solubility without any violation of drug-likeness rules. These findings support the anticancer activity of bioactive metabolites derived from endophytic fungi and provide drug scaffolds and substitute sources for the future development of safe chemotherapy.

Nanoparticles are widely used in many industries such as food and cosmetics. With increasing use, its spread to environmental environments is also increasing. Microalgae have an important place in the uptake of nanoparticles into the food chain. In this study, the effect of TiO2 nanoparticle on antioxidant enzyme activity, malondialdehyde, hydrogen peroxide, chlorophyll-a and total lipid amount in C. vulgaris microalgae has been investigated. As a result of the dose study, while the superoxide dismutase and ascorbate peroxidase enzyme activities decreased, the amount of MDA, H2O2 and chlorophyll-a increased. Depending on the times at different light:dark ratios, both an increase and a decrease occurred in the SOD, APX enzyme activity and the amount of MDA, H2O2. There was an increase in the amount of chlorophyll-a. In the time study, while the SOD and APX enzyme activities increased, the amount of MDA and H2O2 decreased. The amount of chlorophyll-a increased. In the total lipid study, the total lipid amount in the group with nano TiO2 increased compared to the control group. At the same time, C18:2 T (linoleic acid) has been found as fatty acid methyl ester in both groups.

Background: Triple-negative breast cancer (TNBC) is the most serious subtype of breast cancer (BC) and has been a great health threat to females. Although chemotherapeutic agent contributes a lot to TNBC treatment, drug resistance has been a great obstacle for chemotherapies. Ursolic acid (UA), a pentacyclic triterpenoid compound, was reported to reverse paclitaxel resistance in BC. However, whether UA could affect the resistance of TNBC cells to other drugs such as doxorubicin (DOX) remains to be discovered. Materials and Methods: MTT assay, EdU assay, colony formation assay, and flow cytometry analysis were implemented to detect the viability, proliferation, and apoptosis of DOX-resistant MDA-MB-468 and MDA-MB-436 cells with or without UA treatment. Mechanism assays including RIP, RNA pull-down, and luciferase reporter assays verified the interaction between RNAs. Results: UA treatment hindered the growth and mitigated the DOX resistance of DOX-resistant MDA-MB-468 and MDA-MB-436 cells. Mechanistically, multidrug resistance-associated protein 1 (ABCC1) expression was downregulated by UA treatment. MiR-186-5p was verified to target ABCC1. Further, UA-inhibited ZEB1-AS1 (zinc finger E-box binding homeobox 1 antisense RNA 1) was verified as a competitive endogenous RNA (ceRNA) to upregulate ABCC1 through sponging miR-186-5p. Importantly, UA treatment impaired the malignant phenotypes of DOX-resistant MDA-MB-468 and MDA-MB-436 cells through ZEB1-AS1/ABCC1 axis. Conclusion: UA promotes TNBC cell sensitivity to DOX through inactivating ZEB1-AS1/miR-186-5p/ABCC1 signaling.

To our knowledge, this study represents the first demonstration of Arthrographis kalrae biofilm formation in vitro by scanning electron microscopy and the distinct cytotoxic activity between planktonic and biofilm extracts on RAW 264.7 cell line. Higher activity was observed with biofilm. It could impact host immune response, that require furthers study.

The utilization of herbal medicinal plants has gained significant attention for their therapeutic potential in disease treatment and health improvement. Ocimum sanctum, commonly known as Holy Basil or Tulsi, is a medicinal plant with a rich history in traditional medicine, particularly in Ayurveda. The Nanoemulsion was prepared using the ultra-sonication method, and its particle size, Polydispersity index (PDI), and zeta potential was characterized. The phytochemical profile of the Ocimum sanctum seed extract was determined, revealing the presence of flavonoids, phenols, terpenoids, alkaloids, saponins, and glycosides. The extractive yield was found to be 8.9%. The prepared Nanoemulsion exhibited a particle size of 100 nm, a low PDI of 0.245, and a zeta potential of -30 mV, indicating its stability. The in vitro MTT assay demonstrated concentration-dependent cytotoxicity of the Nanoemulsion on human cancer cell lines (HeLa), with higher selectivity towards cancer cells compared to normal cells (HEK-293). Furthermore, the Nanoemulsion showed concentration-dependent inhibition of COX-2, TNF-α, and IL-6 in an in vitro anti-inflammatory assay using peripheral blood mononuclear cells (PBMCs) treated with lipopolysaccharide (LPS). These findings highlight the potential therapeutic applications of the Ocimum sanctum seed Nanoemulsion in the treatment and management of diseases associated with inflammation.

This paper presents a facile and effective method for the large-scale production of carbon dots (CDs) from diverse coconut wastes (fronds, husk and shell). On comparing two different methods, namely (i) hydrothermal carbonization and (ii) novel sequential synthesis processes (pyrolysis followed by sonication), the latter procedure recorded a higher recovery of CDs (14.0%) over the hydrothermal method (2.33%). Doping agents such as urea, polyethyleneimine (PEI) and hexamethylenetetramine (HMTA) were chosen at varying concentrations to synthesize surface-modified CDs (SMCDs) for enhanced antibacterial properties. Among these SMCDs, urea-doped CDs (1:1) @ 1000 ppm registered significantly higher cytotoxicity (20.6%) against Escherichia coli (E. coli). Subsequently, to assess the applicability of CDs as a disinfectant in water purification systems, two products, namely (i) CD-infused chitosan beads and (ii) pelletized CDs, were developed to ensure the immobilization of CDs. Studies with lab-scale prototypes have revealed that CDs infused chitosan beads reduced the colonies of E. coli from 5.41 × 102 CFU/mL (control group) to 2.16 × 102 CFU/mL, in comparison with pelletized CDs that decreased to 3.30 × 102 CFU/mL. The biosafety of CDs was assessed against Eisenia fetida for 21 days, and the observations revealed no mortality, even at 2000 ppm. Overall, this research demonstrated that a waste biomass can be effectively transformed into a novel water disinfectant. Furthermore, this scientific endeavor opens up research avenues to evolve advanced water purifiers using low-cost and eco-friendly nanomaterials.

The alkaloids isolated from Zanthoxylum rhoifolium have demonstrated great pharmacological potential; however, the toxic profiles of these extracts and fractions are still not well elucidated. This study evaluated the toxicity of the ethanol extract (EEZR) and neutral (FNZR) and alkaloid (FAZR) fractions. Chemical characterization was performed by chromatographic methods: thin-layer chromatography (TLC) and high-performance liquid chromatography coupled with diode array detection (HPLC–DAD). The cytotoxicity of the samples was evaluated in human hepatocellular carcinoma (HepG2) cells using the cell viability method (MTT) and mutagenicity by the Allium cepa assay (ACA). Alkaloids isolated from the species were selected for toxicity prediction using preADMET and PROTOX. The molecular docking of the topoisomerase II protein (TOPOII) was used to investigate the mechanism of cell damage. In the EEZR, FNZR, and FAZR, the presence of alkaloids was detected in TCL and HPLC–DAD analyses. These samples showed a 50% inhibitory concentration (IC50) greater than 400 μg/mL in HepG2 cells. In ACA, time- and concentration-dependent changes were observed, with a significant reduction in the mitotic index and an increase in chromosomal aberrations for all samples. Nuclear sprouts and a micronucleus of the positive control (PC) were observed at 10 µg/mL and in the FAZR at 30 µg/mL; a chromosomal bridge in FNZR was observed at 105 µg/mL, CP at a concentration of 40 µg/mL, and nuclear bud and mitotic abnormalities in the EEZR were observed at 170 µg/mL. The alkaloids with a benzophenanthridine were selected for the in silico study, as structural alterations demonstrated certain toxic effects. Molecular docking with topo II demonstrated that all alkaloids bind to the protein. In summary, the fractionation of Z. rhoifolium did not interfere with toxicity; it seems that alkaloids with a benzophenanthridine nucleus may be involved in this toxicity.

Scutellaria multicaulis is a medicinal plant indigenous to Iran, Afghanistan, and Pakistan. It has been widely used as a prominent herb in traditional medicine for thousands of years. This plant is reported to contain baicalein, wogonin, and chrysin flavonoids, which are a significant group of chemical ingredients which can cure different diseases, such as breast cancer. S. multicaulis leaf extract was used for the bioreduction of silver nanoparticles (SmL-Ag-NPs), and their phytochemical contents and antioxidant, antibacterial, anti-proliferative, and apoptotic activity were evaluated. Optimal physicochemical properties of SmL-Ag-NPs were obtained by mixing 5% of leaf extract and 2 mM of aqueous AgNO3 solution and confirmed by characterization studies including UV–visible spectrophotometry, Field Emission Scanning Electron Microscope (FE-SEM), Energy Dispersive X-ray (EDX), Dynamic Light Scattering (DLS), zeta potential, Thermogravimetric analysis (TGA), Surface-enhanced Raman spectroscopy (SERS), X-ray crystallography (XRD), and Fourier transform infrared (FTIR) Spectroscopy. SmL-Ag-NPs exhibited a higher content of total phenol and total flavonoid and potential antioxidant activity. SmL-Ag-NPs also demonstrated dose-dependent cytotoxicity against MDA-MB231 cell multiplication with an IC50 value of 37.62 μg/mL through inducing cell apoptosis. Results show that SmL-Ag-NPs is effective at inhibiting the proliferation of MDA-MB231 cells compared to tamoxifen. This demonstrates that SmL-Ag-NPs could be a bio-friendly and safe strategy to develop new cancer therapies with a reduction in the adverse effects of chemotherapy in the near future.

The study aim was to evaluate the cytotoxic activity, using the MTT test [3-(4,5-Dimethilthiazol-2-yl)-2,5-diphenil tetrazolium bromide], from the crude extract of Picrasma crenata (Pau Tenente) and its isolated compounds, quassin and parain, in culture of rat liver tumor cells (HTC). The test was carried out exposing the cells for 24, 48 and 72 hours to concentrations of 5, 10, 50, 100, 200, 300, 400, 500 and 1000 μg of crude extract of Pau Tenente/mL of culture medium and 1, 5, 10, 15, 20, 40, 60, 80 and 100 μg of quassin or parain compounds/mL of culture medium. The absorbances averages results obtained showed that the crude extract did not present cytotoxicity for the HTC cells in all the concentrations and evaluated times. For quassin, the concentrations of 80 and 100 μg/mL were cytotoxic, after 72 hours of treatment. For parain, the concentrations of 1, 5, 20, 40, 60, 80 and 100 µg/mL, in 72 hours, were cytotoxic, revealing a new activity for this compound. Thus, the results demonstrate a first indication of the cytotoxic activity of compounds quassin and parain, adding an important social and economic value to them, and may have application in future research and in pharmaceutical industry. Resumo O objetivo do estudo foi avaliar a atividade citotóxica, por meio do teste MTT [brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetrazólio], do extrato bruto de Picrasma crenata (Pau Tenente) e seus compostos isolados, quassina e paraína, em cultura de células tumorais de fígado de rato (HTC). O teste foi realizado expondo as células por 24, 48 e 72 horas às concentrações de 5, 10, 50, 100, 200, 300, 400, 500 e 1000 μg de extrato bruto de Pau Tenente/mL de meio de cultura e 1, 5, 10, 15, 20, 40, 60, 80 e 100 μg de compostos de quassina ou paraína/mL de meio de cultura. Os resultados das médias de absorbâncias obtidos mostraram que o extrato bruto não apresentou citotoxicidade para as células HTC em todas as concentrações e tempos avaliados. Para quassina, as concentrações de 80 e 100 μg/mL foram citotóxicas, após 72 horas de tratamento. Para a paraína, as concentrações de 1, 5, 20, 40, 60, 80 e 100 µg/mL, em 72 horas, foram citotóxicas, revelando uma nova atividade para este composto. Assim, os resultados demonstram uma primeira indicação da atividade citotóxica dos compostos quassina e paraína, agregando-lhes importante valor social e econômico, podendo ter aplicação em pesquisas futuras e na indústria farmacêutica.

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy.

Many medicinal plants found in Africa, such as Dovyallis caffra, have been reported to contain various bioactive compounds, which have been found to reduce metal salts into their corresponding metal-based nanoparticles. In this paper, the evaluation of synthesis, characterization, and biological properties of Dovyallis caffra-mediated cassiterite (SnO2) nanoparticles was carried out. The physicochemical properties of the synthesized material were investigated using X-ray diffraction (XRD), energy dispersive X-ray analysis (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. The characterization studies revealed that the material possessed a single tetragonal cassiterite SnO2 phase, having a cluster-like foam appearance and an irregular spherical morphology with diameters ranging from 6.57 to 34.03 nm. The biological screening revealed that the prepared cassiterite (SnO2) nanoparticles exhibited cytotoxicity against the MCF-7 breast cancer cells, with an IC50 value of 62.33 µg mL−1, better than the standard drug 5-fluorouracil, with an IC50 value of 71.21 µg mL−1. The radical scavenging potential of the nanoparticles, using the DPPH assay, showed that it possessed a slightly better activity than ascorbic acid, a common antioxidant. These results suggest that the Dovyallis caffra-mediated cassiterite (SnO2) nanoparticles possess the potential to simultaneously generate and scavenge excess ROS, which in turn results in the exhibition of good cytotoxicity and antioxidant properties.