Search

Epigallocatechin-3-gallate (EGCG) and ascorbic acid (AA)-loaded transferosomes (TRANS) were developed for brain delivery. The investigation covered EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS formulations using the film hydration technique. We analyzed the formed transferosomes to confirm the presence of vesicles loaded with the respective drugs and their performance within a living organism. The sizes of the particles for EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS were measured correspondingly at 174.2 ± 1.80, 132.7 ± 12.22, and 184.31 ± 9.5 nm. The appearance of diffused rings in the scanning electron microscopic image suggests that the payload has a crystalline structure. The atomic force microscope image displayed minimal surface irregularities, potentially indicating the presence of a lipid layer on the surface. Hemolysis results indicated the safety of the vesicles. The results showed 10.23, 7.21, and 8.20% of hemolysis for EGCG-TRANS, AA-TRANS, and EGCG-AA-TRANS, respectively. In the case of EGCG-AA-TRANS, the release of EGCG was determined to be 61.65% ± 4.61 after 72 h when exposed to phosphate buffer saline (pH 7.4). In vivo studies show a good response against Alzheimer's disease (AD). EGCG-AA-TRANS (82.166%) exhibited a higher percentage of AChE inhibition in comparison to EGCG-TRANS (66.550%) and AA-TRANS (53.466%). Intranasal delivery of EGCG-AA-TRANS resulted in approximately a 5-fold enhancement in memory. Formulation allowed EGCG and AA to accumulate in various organs, including the brain. The results suggest that EGCG-AA-TRANS could be safe and effective for treating AD., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Colorectal cancer (CRC) has witnessed a concerning increase in incidence and poses a significant therapeutic challenge due to its poor prognosis. There is a pressing demand to identify novel drug therapies to combat CRC. In this study, we addressed this need by utilizing the pharmacological profiles of anticancer drugs from the Genomics of Drug Sensitivity in Cancer (GDSC) database and developed QSAR models using the Support Vector Machine (SVM) algorithm for prediction of alternative and promiscuous anticancer compounds for CRC treatment. Our QSAR models demonstrated their robustness by achieving a high correlation of determination ( R 2 ) after 10-fold cross-validation. For 12 CRC cell lines, R 2 ranged from 0.609 to 0.827. The highest performance was achieved for SW1417 and GP5d cell lines with R 2 values of 0.827 and 0.786, respectively. Further, we listed the most common chemical descriptors in the drug profiles of the CRC cell lines and we also further reported the correlation of these descriptors with drug activity. The KRFP314 fingerprint was the predominantly occurring descriptor, with the KRFPC314 fingerprint following closely in prevalence within the drug profiles of the CRC cell lines. Beyond predictive modeling, we also confirmed the applicability of our developed QSAR models via in silico methods by conducting descriptor-drug analyses and recapitulating drug-to-oncogene relationships. We also identified two potential anti-CRC FDA-approved drugs, viomycin and diamorphine, using QSAR models. To ensure the easy accessibility and utility of our research findings, we have incorporated these models into a user-friendly prediction Web server named "ColoRecPred", available at https://project.iith.ac.in/cgntlab/colorecpred. We anticipate that this Web server can be used for screening of chemical libraries to identify potential anti-CRC drugs., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Seven-membered homometallic Fe III 7 , Mn III 3 Mn II 4 coordination clusters were previously reported to be spin-frustrated molecular discs. Herein, a mixed bimetallic and mixed-valence dicationic [Mn II Mn III 2 Ni II 4 (N 3 ) 4 (hmp) 10 ](NO 3 ) 2 ( 1 2+ (NO 3 ) 2 ) was isolated in pure form without scrambling of Ni/Mn ions. It was structurally characterized by single-crystal X-ray single-crystal diffraction. The presence of Mn II ions at the center of the disc has been confirmed by EPR measurements. The magnetic studies suggest that complex 1 2+ (NO 3 ) 2 possesses spin frustration with spin ground states S = 17/2 and 19/2, which has been studied and supported by DFT calculation. The purity of 1 2+ (NO 3 ) 2 was confirmed by powder XRD measurements, and the ratio of Ni:Mn = 4:3 was further determined by SEM-EDX analysis., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

This work highlighted the counterion association of diphenhydramine hydrochloride (DPC) and chlorpheniramine maleate (CPM) with anionic sodium tetradecyl sulfate (STS) by conductivity, fluorescence, and UV spectrophotometer measurements. The presence of drugs and the formation of premicellar aggregates of STS were highlighted. The modified Corrin-Harkins CH approaches assessed the STS counterion binding values B = 0.300 for DPC and 0.379 for CPM in the aqueous media at 25 °C. The counterion binding constant (β c ) and Gibb's free energy of micellization (Δ G mic °) were increased and became more negative, suggesting that the drug-surfactant interaction was controlled by electrostatic interaction. Furthermore, the spectral study evaluated that the three isosbestic points for CPM and one isosbestic point for DPC in the STS micelles were observed, which confirmed that CPM was more binding than DPC with the STS micelles. The differential absorbance spectra study was applied to UV spectra to determine the binding constants ( K b ) of 2.232 and 2.837 and partition coefficients ( K x ) of 286.64 and 3209.21 for DPC and CPM in the presence of STS micelles. The findings demonstrated that the CPM molecules have been associated with the Palisade layer of the STS micelles, and the DPC molecules were bound to the Stern layer of the STS micelles. Finally, we came to the conclusion that ionic drugs could improve the micellization capabilities of surfactants, which might be useful for choosing the best excipients for pharmaceutical applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The objective of the research was to identify significant variables that impact the porosity-related properties of CaCO 3 particles. The Placket-Burman design was employed to screen multiple variables, including pH, molar concentrations of calcium chloride and sodium carbonate, temperature, concentration of Gelucire 44/14, Cremophor RH40, Solutol HS15, Labrasol, mixing rate, reaction time, and order of addition. The response variables were surface area, pore radius, and pore volume. Influential methodologies such as XRD, FTIR, Raman spectroscopy, and TGA were utilized to validate the precipitate type. The BET surface area ranged from 1.5 to 16.14 m 2 /g, while the pore radius varied from 2.62 to 6.68 nm, and the pore volume exhibited a range of 2.43 to 37.97 cc/gm. Vaterite structures with spherical mesoporous characteristics were observed at high pH, whereas calcite formations occurred at low pH. The order of addition impacted the surface area but did not affect the pore volume. To maximize the surface area, a lower reaction time and molar concentrations of sodium carbonate were found to be advantageous. The pore radius was influenced by the pH, surfactants, and reaction conditions. The sediments were categorized based on the percentage of vaterite formation. The instrumental techniques effectively characterized the precipitates and provided a valuable complementary analysis., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Carbon dioxide (CO 2 ), a valuable feedstock, can be reutilized as a hydrogen carrier by hydrogenating CO 2 to formic acid (FA) and releasing hydrogen by FA dehydrogenation in a reversible manner. Notably, FA is liquid at room temperature and can be stored and transported considerably more safely than hydrogen gas. Herein, we extensively reviewed transition-metal-based molecular catalysts explored for reversible CO 2 hydrogenation and FA dehydrogenation. This Review describes different approaches explored for carbon-neutral hydrogen storage and release by applying CO 2 hydrogenation to FA/formate and the subsequent release of H 2 by the dehydrogenation of FA over a wide range of molecular catalysts based on noble and non-noble metals. Emphasis is also placed on the specific catalyst-to-substrate interaction by highlighting the specific role of the catalyst in the CO 2 hydrogenation-FA dehydrogenation pathway., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Crystallization has revolutionized the field of solid-state formulations by modulating the physiochemical and release profile of active pharmaceutical ingredients (APIs). Dimethyl fumarate (DF), an FDA-approved first-line drug for relapsing-remitting multiple sclerosis, has a sublimation problem, leading to loss of the drug during its processing. To tackle this problem, DF cocrystal has been prepared by using solvent evaporation technique using nicotinamide as a coformer, which has been chosen based on in silico predictions and their ability to participate in hydrogen bonding. Fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and sublimation analysis have characterized the cocrystal and its thermostability. Comparative analysis of the release profile has been done by the dissolution and pharmacokinetic study of DF and its cocrystal. Formulated cocrystal is noncytotoxic, antioxidant and inhibits interleukin-6 and tissue necrosis factor-α in peripheral blood mononuclear cells induced by lipopolysaccharide. We have obtained a thermostable cocrystal of DF with a similar physicochemical and release profile to that of DF. The formulated cocrystal also provides a gastroprotective effect which helps counterbalance the adverse effects of DF by reducing lipid peroxidation and total nitrite levels., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

This study aimed to prepare colloidosome particles loaded with pyrazinamide (PZA). These drug-loaded colloidosomes were prepared using an in situ gelation technique using a central composite design with a shell made of calcium carbonate (CaCO 3 ) particles. Optimal amounts of 150 mg of CaCO 3 , sodium alginate (2%), and 400 mg of poly(3-hydroxybutyrate- co -3-hydroxy valerate) (PHBV) concentration resulted in the maximum drug loading and efficient release profile. Field emission scanning electron microscopy results showed spherical porous particles with a good coating of the PHBV polymer. Additionally, Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetric and differential thermal analysis (TGA-DTA), and X-ray diffraction (XRD) analysis showed good compatibility between the drug and excipients. The pharmacokinetic studies demonstrated that the drug-loaded colloidosomes resulted in 4.26 times higher plasma drug concentrations with C max values of 32.386 ± 2.744 mcg/mL (PZA solution) and 115.868 ± 53.581 mcg/mL (PZA-loaded colloidosomes) and AUC 0- t values of 61.24 mcg-h/mL (PZA solution) and 260.9 mcg-h/mL (PZA-loaded colloidosomes), indicating that colloidosomes have the potential to be effective drug carriers for delivering PZA to the target site., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

In the present study, we developed and validated a rapid, specific, sensitive, and reproducible liquid chromatography-electrospray ionization tandem mass spectrometry method for quantifying quercetin (QT) in rabbit plasma using hydrochlorothiazide as the internal standard. Animals were orally administered with optimized QT-loaded nanoemulsion (QTNE) and QT suspension (QTS), equivalent to 30 mg/kg, to the test and control group, respectively. The blood samples were collected at pre-determined time points up to 48 h. The linearity range was from 5 to 5000 ng mL -1 with R 2 = 0.995. Further, we analyzed the various pharmacokinetic parameters and established the in vitro - in vivo correlation (IVIVC) of QTNE using GastroPlus software. The method was successfully developed and validated, and when applied for the determination of QT in rabbit plasma, it exhibited an increase in C max from 122.56 ng mL -1 (QTS) to 286.51 ng mL -1 (QTNE) (2.34-fold) and AUC 0-48 from 976 ng h mL -1 (QTS) to 4249 ng h mL -1 (QTNE) (4.35-fold), indicating improved oral bioavailability QT when administered as QTNE. Statistical analysis revealed that the Loo-Riegelman method (two-compartmental method) best fitted the deconvolution approach ( R 2 = 0.998, SEP = 4.537, MAE = 2.759, and AIC = 42.38) for establishing the IVIVC. In conclusion, the established bioanalytical method and IVIVC studies revealed that QTNE is a potential carrier for the effective delivery of QT with enhanced oral bioavailability., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

A library of 57 compounds of natural andrographolide was designed, synthesized, and screened for in vitro studies against four human cancer cell lines: A594, PC-3, MCF-7, and HCT-116. Most of the synthesized compounds displayed better cytotoxic profile against all tested cells compared to the parent andrographolide ( 1 ). The tested semisynthetic derivatives of andrographolide were found to be more sensitive toward lung carcinoma (A594) and prostate carcinoma (PC-3) cell lines. Among the synthesized compounds, the C-17 p -methoxy phenyl ester analog 8s inhibited cell proliferation effectively in A549 (IC 50 : 6.6 μM) and PC-3 (IC 50 : 5.9 μM) cell variants, and compound 9s exhibited the most potent activity against the A594 cell line, with an IC 50 value of 3.5 μM. Further anticancer mechanistic investigation demonstrated that compound 9s displayed nuclear morphological changes and increased reactive oxygen species (ROS) with disturbed mitochondrial membrane potential (MMP) that can lead to apoptosis. To know the exact structure confirmation of intermediate compounds 4 and 5 , single X-ray crystallography was performed, which supported the complete reaction design of this work., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Fungal endophytes are known to be a paragon for producing bioactive compounds with a variety of pharmacological importance. The current study aims to elucidate the molecular alterations induced by the bioactive compounds produced by the fungal endophyte Colletotrichum gloeosporioides in the tumor microenvironment of human breast cancer cells. GC/MS analysis of the ethyl acetate (EA) extract of C. gloeosporioides revealed the presence of bioactive compounds with anticancer activity. The EA extract of C. gloeosporioides exerted potential plasmid DNA protective activity against hydroxyl radicals of Fenton's reagent. The cytotoxic activity further revealed that MDA-MB-231 cells exhibit more sensitivity toward the EA extract of C. gloeosporioides as compared to MCF-7 cells, whereas non-toxic to non-cancerous HEK293T cells. Furthermore, the anticancer activity demonstrated by the EA extract of C. gloeosporioides was studied by assessing nuclear morphometric analysis and induction of apoptosis in MDA-MB-231 and MCF-7 cells. The EA extract of C. gloeosporioides causes the alteration in cellular and nuclear morphologies, chromatin condensation, long-term colony inhibition, and inhibition of cell migration and proliferation ability of MDA-MB-231 and MCF-7 cells. The study also revealed that the EA extract of C. gloeosporioides treated cells undergoes apoptosis by increased production of reactive oxygen species and significant deficit in mitochondrial membrane potential. Our study also showed that the EA extract of C. gloeosporioides causes upregulation of pro-apoptotic ( BAX , PARP , CASPASE-8 , and FADD ), cell cycle arrest ( P21 ), and tumor suppressor ( P53 ) related genes. Additionally, the downregulation of antiapoptotic genes ( BCL-2 and SURVIVIN ) and increased Caspase-3 activity suggest the induction of apoptosis in the EA extract of C. gloeosporioides treated MDA-MB-231 and MCF-7 cells. Overall, our findings suggest that the bioactive compounds present in the EA extract of C. gloeosporioides promotes apoptosis by altering the genes related to the extrinsic as well as the intrinsic pathway. Further in vivo study in breast cancer models is required to validate the in vitro observations., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Carcinoma of the lungs is among the most menacing forms of malignancy and has a poor prognosis, with a low overall survival rate due to delayed detection and ineffectiveness of conventional therapy. Therefore, drug delivery strategies that may overcome undesired damage to healthy cells, boost therapeutic efficacy, and act as imaging tools are currently gaining much attention. Advances in material science have resulted in unique nanoscale-based theranostic agents, which provide renewed hope for patients suffering from lung cancer. Nanotechnology has vastly modified and upgraded the existing techniques, focusing primarily on increasing bioavailability and stability of anti-cancer drugs. Nanocarrier-based imaging systems as theranostic tools in the treatment of lung carcinoma have proven to possess considerable benefits, such as early detection and targeted therapeutic delivery for effectively treating lung cancer. Several variants of nano-drug delivery agents have been successfully studied for therapeutic applications, such as liposomes, dendrimers, polymeric nanoparticles, nanoemulsions, carbon nanotubes, gold nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, hydrogels, and micelles. In this Review, we present a comprehensive outline on the various types of overexpressed receptors in lung cancer, as well as the various targeting approaches of nanoparticles., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Amino acid-surfactant interactions are central to numerous studies because of their increased effectiveness in chemical, biological, household and industrial use. This review will focus on the impact and effect of the physicochemical properties, temperature, pH, and surfactant chain length of the amino acid for detailed exploration of amino acids and surfactants in aqueous medium. The impact of cosolvent on self-aggregation, critical micelle concentration (CMC), and binding affinity with other biomolecules, as well as amino acid-surfactant interactions, are the epicenters. The results show that increasing the temperature causes negative enthalpy for ionic surfactants and micellization, implying that micellization and amino acids are thermodynamically spontaneous and exothermic, accompanied by positive entropy. As these physicochemical studies are additive, the amino acid and ionic surfactant interactions provide clues on protein unfolding and denaturation under different media, which further changes with a change in physiological conditions like pH, cosolvent, chain length, and temperature. On varying the pH, the net charge of the amino acid also changes and, subsequently, the binding efficiency of the amino acids to the surfactants. The presence of cosolvent causes a lowering in the hydrophobic chain, which changes the surfactant's CMC. At a reduced CMC, the hydrophobic characteristic of amino acid-surfactant associations is amplified, leading to rapid denaturation of proteins that act as propulsion under the influence of extended chain surfactants. Amino acids are one of the most intriguing classes of chemicals that produce high inhibitory efficacy. Amino acids are also a component of proteins and therefore, found in a significant part of the human body, further making them a promising candidate as corrosion inhibitors. In this review article, authors have also focused on the collection and investigation for application of amino acid-surfactant interactions in corrosion inhibition. Various predictive studies/ in silico studies are also reported by many research groups, such as density functional theory (DFT) calculations and molecular dynamics simulations to obtain tentative electronic, structural, and physiochemical characteristics like energies of the highest occupied molecular orbitals and lowest unoccupied molecular orbitals, binding energy, Gibb's free energy, electronegativity, polarizability, and entropy. In silico studies are helpful for the mechanism predictions of the process occurring on metal surfaces., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A green-based approach for the synthesis of silver nanoparticles has gained tremendous attention in biomedical applications. Fungal endophytes have been recognized as a remarkable biological source for the synthesis of potential nanodrugs. The present study focuses on the fabrication of silver nanoparticles using the fungal endophyte Penicillium oxalicum (POAgNPs) associated with the leaf of the Amoora rohituka plant. Sharp UV-visible spectra at 420 nm appeared due to the surface plasmon resonance of POAgNPs and the reduction of silver salt. FT-IR analysis revealed the presence of functional groups of bioactive compounds of P. oxalicum responsible for the reduction of silver salt and validated the synthesis of POAgNPs. A high degree of crystallinity was revealed through XRD analysis, and microscopy-based characterizations such as AFM, TEM, and FESEM showed uniformly distributed, and spherically shaped nanoparticles. Furthermore, POAgNPs showed a potential inhibitory effect against bacterial and fungal strains of pathogenic nature. POAgNPs also exhibited potential antioxidant activity against the synthetically generated free radicals such as DPPH, superoxide, hydroxyl, and nitric oxide with EC 50 values of 9.034 ± 0.449, 56.378 ± 1.137, 34.094 ± 1.944, and 61.219 ± 0.69 μg/mL, respectively. Moreover, POAgNPs exhibited cytotoxic potential against the breast cancer cell lines, MDA-MB-231 and MCF-7 with IC 50 values of 20.080 ± 0.761 and 40.038 ± 1.022 μg/mL, respectively. POAgNPs showed anticancer potential through inhibition of wound closure and by altering the nuclear morphology of MDA-MB-231 and MCF-7 cells. Further anticancer activity revealed that POAgNPs induced apoptosis in MDA-MB-231 and MCF-7 cells by differential expression of genes related to apoptosis, tumor suppression, and cell cycle arrest and increased the level of Caspase-3. The novel study showed that P. oxalicum -mediated silver nanoparticles exhibit potential biological activity, which can be exploited as nanodrugs in clinical applications., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The mammalian transcription termination factor 1 (TTF1) is an essential protein that plays diverse cellular physiological functions like transcription regulation (both initiation and termination), replication fork blockage, chromatin remodeling, and DNA damage repair. Hence, understanding the structure and mechanism conferred by its variable conformations is important. However, so far, almost nothing is known about the structure of either the full-length protein or any of its domains in isolation. Since the full-length protein even after multiple attempts could not be purified in soluble form, we have codon optimized, expressed, and purified the N-terminal 190 amino acid deleted TTF1 (ΔN190TTF1) protein. In this study, we characterized this essential protein by studying its homogeneity, molecular size, and secondary structure using tools like dynamic light scattering (DLS), circular dichroism (CD) spectroscopy, Raman spectroscopy, and atomic force microscopy (AFM). By CD spectroscopy and DLS, we confirmed that the purified protein is homogeneous and soluble. CD spectroscopy also revealed that ΔN190TTF1 is a helical protein, which was further established by analysis of Raman spectra and amide I region deconvolution studies. The DLS study estimated the size of a single protein molecule to be 17.2 nm (in aqueous solution). Our structural and biophysical characterization of this essential protein will open avenues toward solving the structure to atomic resolution and will also encourage researchers to investigate the mechanism behind its diverse functions attributed to its various domains., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Selective permeability of the blood-brain barrier restricts the treatment efficacy of neurologic diseases. Berberine (BBR) and curcumin (CUR)-loaded transferosomes (TRANS) were prepared for the effective management of Alzheimer's disease (AD). The study involved the syntheses of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS by the film hydration method. Vesicles were characterized to ensure the formation of drug-loaded vesicles and their in vivo performance. The particle sizes of BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS were 139.2 ± 7, 143.4 ± 8, and 165.3 ± 6.5 nm, respectively. The presence of diffused rings in the SED image indicates the crystalline nature of the payload. Low surface roughness in an AFM image could be associated with the presence of a surface lipid. BBR-CUR-TRANS showed 41.03 ± 1.22 and 47.79 ± 3.67% release of BBR and 19.22 ± 1.47 and 24.67 ± 1.94% release of CUR, respectively, in phosphate buffer saline (pH 7.4) and acetate buffer (pH 4.0). Formulations showed sustained release of both loaded drugs. BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS exhibited a lower percentage of hemolysis than pure BBR and CUR, indicating the safety of the payload from delivery vesicles. Lower percentages of binding were recorded from BBR-CUR-TRANS than BBR-TRANS and CUR-TRANS. Acetylcholinesterase inhibition activity of the prepared transferosomes was greater than that of pure drugs, which are thought to have good cellular penetration. The spatial memory was improved in treated mice models. The level of malondialdehyde decreased in AD animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS, respectively, as compared to the scopolamine-induced AD animals. BBR-CUR-TRANS-treated animals showed the highest decrease in the NO level. The catalase level was significantly restored in scopolamine-intoxicated animals treated with BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS. The immunohistochemistry result suggested that the BBR-TRANS, CUR-TRANS, and BBR-CUR-TRANS have significantly decreased the regulation of expression of BACE-1 through antioxidant activity. In conclusion, the study highlights the utility of formulated transferosomes as promising carriers for the co-delivery of drugs to the brain., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 μM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin ( 10 ) has shown reduced growth between 0 and 24%. Compounds showing more than 50% growth inhibition were further evaluated for the IC 50 value. Among the cell lines tested, lung cancer cell lines (A549, NCI-H460) were found to be more susceptible toward most of the synthesized compounds. Compounds 14g and 14j demonstrated good antiproliferative activity in NCI-H460 with IC 50 values of 6.65 and 5.55 μM, respectively, while compounds 18b , 18c , 18f , and 18m demonstrated potential antiproliferative activity in A549 cell lines with IC 50 values ranging between 2.9 and 10.5 μM. Among the compounds, compound 18f was found to demonstrate the best activity with an IC 50 value of 2.91 μM against A549. Furthermore, 18f induces cell cycle arrest at the S-phase and disrupts the mitochondrial membrane potential, reducing cell migration potential by inducing cellular apoptosis and higher ROS generation along with a decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as a reduction in the number and shrinkage of cells coupled with nuclear blabbing indicating the sign of apoptosis of A549 non-small cell lung cancer cell lines. Compound 18f has emerged as a lead molecule and may serve as a template for further discovery of capsaicinoid scaffolds., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The Rosellinia sanctae - cruciana extract was subjected to detailed liquid chromatography tandem mass spectrometry studies. A total of 38 peaks were annotated to m / z 508.26, m / z 510.28, m / z 524.26, m / z 526.28, m / z 540.26, m / z 542.27, and m / z 584.28 [M + H] + . The accurate mass, mutually supported UV/vis spectra, and database search identified these compounds as cytochalasins. Systematic dereplication helped identify a peak at m / z 540.26 [M + H] + as the new compound. Further, the identified compound was purified by high-performance liquid chromatography and characterized by 2D NMR to be 19,20-epoxycytochalasin N1, a new optical isomer of 19,20-epoxycytochalasin-N. It exhibited substantial cytotoxicity with IC 50 values ranging from 1.34 to 19.02 μM. This study shows a fast approach for dereplicating and identifying novel cytochalasin metabolites in crude extracts., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Glioblastoma (GBM) is the most devastating and frequent type of primary brain tumor with high morbidity and mortality. Despite the use of surgical resection followed by radio- and chemotherapy as standard therapy, the progression of GBM remains dismal with a median overall survival of <15 months. GBM embodies a populace of cancer stem cells (GSCs) that is associated with tumor initiation, invasion, therapeutic resistance, and post-treatment reoccurrence. However, understanding the potential mechanisms of stemness and their candidate biomarkers remains limited. Hence in this investigation, we aimed to illuminate potential candidate hub genes and key pathways associated with the pathogenesis of GSC in the development of GBM. The integrated analysis discovered differentially expressed genes (DEGs) between the brain cancer tissues (GBM and GSC) and normal brain tissues. Multiple approaches, including gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were employed to functionally annotate the DEGs and visualize them through the R program. The significant hub genes were identified through the protein-protein interaction network, Venn diagram analysis, and survival analysis. We observed that the upregulated DEGs were prominently involved in the ECM-receptor interaction pathway. The downregulated genes were mainly associated with the axon guidance pathway. Five significant hub genes (CTNNB1, ITGB1, TNC, EGFR, and SHOX2) were screened out through multiple analyses. GO and KEGG analyses of hub genes uncovered that these genes were primarily enriched in disease-associated pathways such as the inhibition of apoptosis and the DNA damage repair mechanism, activation of the cell cycle, EMT (epithelial-mesenchymal transition), hormone AR (androgen receptor), hormone ER (estrogen receptor), PI3K/AKT (phosphatidylinositol 3-kinase and AKT), RTK (receptor tyrosine kinase), and TSC/mTOR (tuberous sclerosis complex and mammalian target of rapamycin). Consequently, the epigenetic regulatory network disclosed that hub genes played a vital role in the progression of GBM. Finally, candidate drugs were predicted that can be used as possible drugs to treat GBM patients. Overall, our investigation offered five hub genes (CTNNB1, ITGB1, TNC, EGFR, and SHOX2) that could be used as precise diagnostic and prognostic candidate biomarkers of GBM and might be used as personalized therapeutic targets to obstruct gliomagenesis., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Silk cocoon fibers (SFs) are natural polymers that are made up of fibroin protein. These natural fibers have higher mechanical stability and good elasticity properties. In this work, we coated multiwalled carbon nanotubes (MWCNTs) on the surface of SFs using a simple stirring technique with vinegar as the medium. This SF-MWCNT micro-/nanofiber composite was prepared without any adhesives. The characterization results revealed that the SF-MWCNT micro-/nanofiber composite exhibited excellent electrical conductivity (995 Ω cm -1 ), tensile strength (up to 200% greater elongation), and durability characteristics. In addition, this micro-/nanofiber composite shows a change in resistance from 1450 to 960 Ω cm -1 for an applied mechanical force of 0.3-1 N kg -1 . Based on our findings, SF-MWCNT micro-/nanofiber composite-based conductive fibers (CFs) and force sensors (FSs) were developed., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

d-Glucosamine, a natural, inexpensive, and conveniently accessible sugar, has been explored as an efficient ligand for the Cu(I)-catalyzed regio- and stereoselective synthesis of an array of ( Z )-3-methyleneisoindoline-1-ones and ( E )- N -aryl-4 H -thiochromen-4-imines in good-to-excellent yield in a tandem fashion via the reaction of 2-halobenzamide and 2-halobenzothioamide with terminal alkynes, respectively. The water solubility and biocompatible nature of the ligand offer easy separation of the catalytic system toward the aqueous phase as well as change in the reaction path in terms of the product also demonstrated the variation of the reaction temperature. The domino reaction proceeds by the Sonogashira and Ullmann type cross-coupling reaction, followed by Cu(I)-promoted additive cyclization of heteroatom to the triple bond. In addition, d-glucosamine causes successful Glaser-Hay coupling of terminal alkynes under Cu catalysis to produce a high yield of respective 1,3-diynes., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

The most prevalent and common sexually transmitted infection is caused by human papillomavirus (HPV) among sexually active women. Numerous genotypes of HPV are available, among which the major oncoproteins E6 and E7 lead to the progression of cervical cancer. The E7 oncoprotein interacts with cytoplasmic tumor suppressor protein PTPN14, which is the key regulator of cellular growth control pathways effecting the reduction of steady-state level. Disrupting the interaction between the tumor suppressor and the oncoprotein is vital to cease the development of cancer. Hence, the mechanism of interaction between E7 and tumor suppressor is explored through protein-protein and protein-ligand binding along with the conformational stability studies. The obtained results state that the LXCXE domain of HPV E7 of high and low risks binds with the tumor suppressor protein. Also, the small molecules bind in the interface of E7-PTPN14 that disrupts the interaction between the tumor suppressor and oncoprotein. These results were further supported by the dynamics simulation stating the stability over the bounded complex and the energy maintained during postdocking as well as postdynamics calculations. These observations possess an avenue in the drug discovery that leads to further validation and also proposes a potent drug candidate to treat cervical cancer caused by HPV., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Seven cytochalasins, 19,20-epoxycytochalasin N, cytochalasin P1, deacetyl 19,20-epoxycytochalasin C, 19,20-epoxycytochalasin D, 19,20-epoxycytochalasin C, cytochalasin D, and cytochalasin C, were isolated from a fungal ( Rosellinia sanctae-cruciana ) crude extract. A cytotoxicity assay (sulforhodamine B) was performed on a series of cancer cell lines: HT-29, A-549, PC-3, HCT-116, SW-620, and MCF-7. Simultaneously, the liquid chromatography-mass spectrometry (LC-MS)/MS profile of 19,20-epoxycytochalasin C-treated cell lines revealed that 19,20-epoxycytochalasin C ( m / z 524.25) oxidized to a metabolite of m / z 522.25 Da (-2 Da (-2H) from 19,20-epoxycytochalasin C). Further chemical oxidation of 19,20-epoxycytochalasin C using the Dess-Martin reagent produced an identical metabolite. It has been noticed that the parent molecule (19,20-epoxycytochalasin C) showed an IC 50 of 650 nM (on HT-29), whereas for the oxidized metabolite ( m / z 522.24) of 19,20-epoxycytochalasin C, the IC 50 was >10 μM. It is clear that the parent molecule had 16 times higher cytotoxic potential as compared to the oxidized metabolite. The spectroscopic investigation indicated that the oxidation of the hydroxyl (-OH) group occurred at the C7 position in 19,20-epoxycyctochalsin C and led to the inactivation of 19,20-epoxycytochalasin C. Further, cell cycle analysis and histopathological evidence support the findings, and CDK2 could be a possible target of 19,20-epoxycyctochalasin C., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), 1 H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH 4 . The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy., Competing Interests: The authors declare no competing financial interest., (© 2020 The Authors. Published by American Chemical Society.)

A new secalonic acid derivative, F-7 ( 1 ), was isolated from the endophytic Aspergillus aculeatus MBT 102, associated with Rosa damascena . The planar structure of 1 was established on the basis of 1D and 2D NMR and ESI-TOF-MS spectra. The relative configuration of 1 was determined applying a combined quantum mechanical/NMR approach and, afterward, the comparison of calculated and experimental electronic circular dichroism spectra determined the assignment of its absolute configuration. The compound possesses strong cytotoxic activity against triple negative breast cancer (TNBC) cells. It was found to induce apoptosis, as evidenced by scanning electron microscopy and phase contrast microscopy. Furthermore, flow cytometry analyses demonstrated that 1 induced mitochondrial damage and reactive oxygen species mediated apoptosis, arresting the G1 phase of the cells in a dose-dependent manner. Also, the compound causes significant microtubule disruption in TNBC cells. Subsequently, 1 restricted the cell migration leading to the concomitant increase in expression of cleaved caspase and PARP., Competing Interests: The authors declare no competing financial interest.

Composite materials have revealed remarkable activities in various catalytic applications. However, choosing an appropriate material to enhance the catalytic activity and stability is a major challenge in the field of catalysis. In this article, we reported vanadium phosphorus oxide (VPO)/β-SiC as a stable composite material with good catalytic activity. VPO/β-SiC composite materials with different compositions were fabricated by the impregnation technique to investigate the catalytic activity and stability of these materials in liquid-phase reactions. The physiochemical characteristics of the prepared catalysts were analyzed by several spectroscopic methods. The catalytic activities of VPO/β-SiC composites were studied in a solvent-free oxidation of methanol using tert -butyl hydroperoxide (TBHP) as an oxidant. The reaction conditions were optimized by changing various reaction parameters. Under optimized reaction conditions, the 10 wt % VPO/β-SiC composite showed 100% conversion with 89.8% selectivity to formaldehyde., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Since 2007, repeated outbreaks of Zika virus (ZIKV) have affected millions of people worldwide and created a global health concern with major complications like microcephaly and Guillain Barre's syndrome. To date, there is not a single Zika-specific licensed drug present in the market. However, in recent months, several antiviral molecules have been screened against ZIKV. Among those, (-)-epigallocatechin-3-gallate (EGCG), a green tea polyphenol, has shown great virucidal potential against flaviviruses including ZIKV. The mechanistic understanding of EGCG-targeting viral proteins is not yet entirely deciphered except that little is known about its interaction with viral envelope protein and viral protease. We designed our current study to find inhibitory actions of EGCG against ZIKV NS3 helicase. NS3 helicase performs a significant role in viral replication by unwinding RNA after hydrolyzing NTP. We employed molecular docking and simulation approach and found significant interactions at the ATPase site and also at the RNA binding site. Further, the enzymatic assay has shown significant inhibition of NTPase activity with an IC 50 value of 295.7 nM and Ki of 0.387 ± 0.034 μM. Our study suggests the possibility that EGCG could be considered as a prime backbone molecule for further broad-spectrum inhibitor development against ZIKV and other flaviviruses., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

A series of low-molecular-weight gelators based on an isoxazole backbone were synthesized, which showed robust and phase-selective gelation of a series of oils. Due to their excellent phase-selective and cogelation properties, they were employed for the separation of bisphenol and the recovery of oil spills from water. The driving force and morphology of these gels were characterized by spectroscopic and microscopic studies., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

In India, the major crop is wheat. Its production is severely hampered by seed-borne diseases such as smut and bunt which are responsible for the reduction of crop yield with poor grain quality. In the current study, an attempt was made to prepare a photoluminescence (PL)-based immunosensor for early detection of Karnal bunt (KB) disease. The KB disease-causing pathogen Tilletia indica was detected using functionalized diatom frustules as a sensing platform. The teliospore-covered platform, on exposure to light, showed enhanced intensity of PL in comparison to control. This response was directly proportional to the concentration of spores. For the development of a stable frustule-based immunosensor platform, gluteraldehyde was added for the covalent immobilization of the T. indica antibody onto amine-functionalized diatom substrates. Frustules of diatom consisting of a nanoporous three-dimensional biogenic silica material exhibit a unique property of emitting strong, visible blue PL under ultraviolet (UV) excitation. PL studies were done to reveal the specificity and binding of the conjugated diatom platform that will distinguish between the T. indica (complementary) and A. niger (noncomplementary) antigens. Four times better intensity of PL was observed against the complementary one in comparison to a noncomplementary setup (control). The immunocomplex frustule-based platform serves as a suitable sensor platform for early detection of KB., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Modifications at the carbohydrate moiety of neoandrographolide, isolated from the medicinal plant Andrographis paniculata , result in more potent and less toxic derivatives, namely, 4',6'-benzylidene neoandrographolide ( 2b ) and 4'6'- p -methoxybenzylidene neoandrographolide ( 2c ). These showed improved cytotoxicity against SW-620, PC-3, and A549 cancer cell lines. Nuclear morphology studies were conducted on compound 2b by 4',6-diamidino-2-phenylidole staining and detection of intracellular reactive oxygen species (ROS) accumulation. It showed an increase in the generation of cellular and mitochondrial ROS level. The probable relation of B-cell lymphoma-2 (Bcl-2, an apoptosis inhibitor) to B-cell lymphoma-2-associated X protein (Bax, an apoptosis promoter) ratio with caspase-3 (apoptosis coordination enzyme) in the colon cancer cell line SW-620 was investigated, and it was discovered that upon 2b treatment, the expression of caspase-3 Bax increased remarkably. However, in 2b- treated cells, the expression of Bcl-2 was downregulated as compared to untreated cells., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Electrochemical water splitting is the most energy-efficient technique for producing hydrogen and oxygen, the two valuable gases. However, it is limited by the slow kinetics of the anodic oxygen evolution reaction (OER), which can be improved using catalysts. Covalent organic framework (COF)-derived porous carbon can serve as an excellent catalyst support. Here, we report high electrocatalytic activity of two composites, formed by supporting RuO 2 on carbon derived from two COFs with closely related structures. These composites catalyze oxygen evolution from alkaline media with overpotentials as low as 210 and 217 mV at 10 mA/cm 2 , respectively. The Tafel slopes of these catalysts (65 and 67 mV/dec) indicate fast kinetics compared to commercial RuO 2 . The observed activity is the highest among all RuO 2 -based heterogeneous OER catalysts-a touted benchmark OER catalyst. The high catalytic activity arises from the extremely small-sized (∼3-4 nm) RuO 2 nanoparticles homogeneously dispersed in a micro-mesoporous (BET = 517 m 2 /g) COF-derived carbon. The porous graphenic carbon favors mass transfer, while its N-rich framework anchors the catalytic nanoparticles, making it highly stable and recyclable. Crucially, the soft pyrolysis of the COF enables the formation of porous carbon and simultaneous growth of small RuO 2 particles without aggregation., Competing Interests: The authors declare no competing financial interest.

Zika virus is a mosquito-transmitted flavivirus that causes devastating fetal outcomes in the context of maternal infection during pregnancy. An important target for drugs combatting Zika virus pathogenicity is NS2B-NS3 protease, which plays an essential role in hydrolysis and maturation of the flavivirus polyprotein. We identify hydroxychloroquine, a drug that already has approved uses in pregnancy, as a possible inhibitor of NS2B-NS3 protease by using a Food and Drug Administration-approved drug library, molecular docking, and molecular dynamics simulations. Further, to gain insight into its inhibitory potential toward NS2B-NS3 protease, we performed enzyme kinetic studies, which revealed that hydroxychloroquine inhibits protease activity with an inhibition constant ( K i ) of 92.34 ± 11.91 μM. Additionally, hydroxychloroquine significantly decreases Zika virus infection in placental cells., Competing Interests: The authors declare no competing financial interest.

Core-shell ZIF-8@ZIF-67- and ZIF-67@ZIF-8-based zeolitic imidazolate frameworks (ZIFs) were synthesized solvothermally using a seed-mediated methodology. Transmission electron microscopy-energy-dispersive X-ray spectrometry, line scan, elemental mapping, X-ray photoelectron spectroscopy, and inductively coupled plasma-atomic emission spectroscopy analyses were performed to confirm the formation of a core-shell structure with the controlled Co/Zn elemental composition of ∼0.50 for both the core-shell ZIFs. The synthesized core-shell ZIF-8@ZIF-67 and ZIF-67@ZIF-8 frameworks conferred enhanced H 2 (2.03 and 1.69 wt %) storage properties at 77 K and 1 bar, which are ca. 41 and 18%, respectively, higher than that of the parent ZIF-8. Notably, the distinctly remarkable H 2 storage properties shown by both the core-shell ZIFs over the bimetallic Co/Zn-ZIF and the physical mixture of ZIF-8 and ZIF-67 clearly evidenced their unique structural properties (confinement of porosity) and elemental heterogeneity due to the core-shell morphology of the outperforming core-shell ZIFs. Moreover, H 2 adsorption isotherm data of these frameworks are best fitted with the Langmuir model ( R 2 ≥ 0.9999). Along with the remarkably enhanced H 2 storage capacities, the core-shell ZIFs also displayed an improved CO 2 capture behavior. Hence, we demonstrated here that the controlled structural features endorsed by the rationally designed porous materials may find high potential in H 2 storage applications., Competing Interests: The authors declare no competing financial interest.