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Dacarbazine is an anticancer drug used in the treatment of skin melanoma. However, its systemic administration results in various side effects. These constraints might be alleviated by topical dacarbazine administration for the treatment of skin melanoma, although it is confined by the drug's limited skin permeability. To improve dacarbazine efficacy against skin cancer and minimize its systemic side effects, it was loaded in lipid polymer hybrid nanoparticle (LPHN)-based topical delivery system. LPHNs were prepared using emulsification solvent evaporation method employing experimental design for the optimization of independent variables. Optimized LPHNs showed particle size, entrapment efficiency, and zeta potential of 202.7 nm, 70.29 ± 0.97%, and − 24.89 mV, respectively. Further, optimized formulation was incorporated in gel and was evaluated for ex vivo permeability. Studies revealed enhanced permeability following Higuchi diffusion kinetics. Flux was observed to be 15.93 ± 1.61 μg·cm−2·h−1. Anticancer efficacy studies on melanoma cell line exhibited enhanced cytotoxicity of drug. Accelerated stability studies indicated stability of drug for at least six months. These results confirm the potential of topical dacarbazine LPHNs to enhance the efficacy against skin melanoma. [ABSTRACT FROM AUTHOR]

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior. [ABSTRACT FROM AUTHOR]

Abstract In this study, two new molecules were synthesized from the reaction of 2-methyl-1H-benzo[d]imidazole with aryl halides in the presence of a strong base. The structures newly of synthesized 1,2-disubstituted benzimidazole compounds were characterized using spectroscopic techniques (FT-IR, 1HNMR, 13CNMR) and chromatographic technique (LC/MS). For discovering an effective anticancer drug, the developed heterocyclic compounds were screened against three different human cancer cell lines (A549, DLD-1, and L929). The results demonstrated that of IC50 values of compound 2a were higher as compared to cisplatin for the A549 and DLD-1 cell lines. The frontier molecular orbital (FMO), and molecular electrostatic potential map (MEP) analyses were studied by using DFT (density functional theory) calculations at B3LYP/6-31G** level of theory. The molecular docking studies of the synthesized compound with lung cancer protein, PDB ID: 1M17, and colon cancer antigen proteins, PDB ID: 2HQ6 were performed to compare with experimental and theoretical data. Compound 2a had shown the best binding affinity with -6.6 kcal/mol. It was observed that the theoretical and experimental studies carried out supported each other.

The increasing emergence of multidrug-resistant (MDR) pathogens due to antibiotic misuse translates into obstinate infections with high morbidity and high-cost hospitalizations. To oppose these MDR superbugs, new antimicrobial options are necessary. Although both quaternary ammonium salts (QASs) and phosphonium salts (QPSs) possess antimicrobial effects, QPSs have been studied to a lesser extent. Recently, we successfully reported the bacteriostatic and cytotoxic effects of a triphenyl phosphonium salt against MDR isolates of the Enterococcus and Staphylococcus genera. Here, aiming at finding new antibacterial devices possibly active toward a broader spectrum of clinically relevant bacteria responsible for severe human infections, we synthesized a water-soluble, sterically hindered quaternary phosphonium salt (BPPB). It encompasses two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying the characteristics of molecules known as bola-amphiphiles. BPPB was characterized by ATR-FTIR, NMR, and UV spectroscopy, FIA-MS (ESI), elemental analysis, and potentiometric titrations. Optical and DLS analyses evidenced BPPB tendency to self-forming spherical vesicles of 45 nm (DLS) in dilute solution, tending to form larger aggregates in concentrate solution (DLS and optical microscope), having a positive zeta potential (+18 mV). The antibacterial effects of BPPB were, for the first time, assessed against fifty clinical isolates of both Gram-positive and Gram-negative species. Excellent antibacterial effects were observed for all strains tested, involving all the most concerning species included in ESKAPE bacteria. The lowest MICs were 0.250 µg/mL, while the highest ones (32 µg/mL) were observed for MDR Gram-negative metallo-β-lactamase-producing bacteria and/or species resistant also to colistin, carbapenems, cefiderocol, and therefore intractable with currently available antibiotics. Moreover, when administered to HepG2 human hepatic and Cos-7 monkey kidney cell lines, BPPB showed selectivity indices > 10 for all Gram-positive isolates and for clinically relevant Gram-negative superbugs such as those of E. coli species, thus being very promising for clinical development. [ABSTRACT FROM AUTHOR]

In this study, two new molecules were synthesized from the reaction of 2-methyl-1H-benzo[d]imidazole with aryl halides in the presence of a strong base. The structures newly of synthesized 1,2-disubstituted benzimidazole compounds were characterized using spectroscopic techniques (FT-IR, 1HNMR, 13CNMR) and chromatographic technique (LC/MS). For discovering an effective anticancer drug, the developed heterocyclic compounds were screened against three different human cancer cell lines (A549, DLD-1, and L929). The results demonstrated that of IC50 values of compound 2a were higher as compared to cisplatin for the A549 and DLD-1 cell lines. The frontier molecular orbital (FMO), and molecular electrostatic potential map (MEP) analyses were studied by using DFT (density functional theory) calculations at B3LYP/6-31G** level of theory. The molecular docking studies of the synthesized compound with lung cancer protein, PDB ID: 1M17, and colon cancer antigen proteins, PDB ID: 2HQ6 were performed to compare with experimental and theoretical data. Compound 2a had shown the best binding affinity with -6.6 kcal/mol. It was observed that the theoretical and experimental studies carried out supported each other. [ABSTRACT FROM AUTHOR]

The efficacy of dasatinib (DAS) in treating hepatocellular carcinoma (HCC) is hindered by its poor bioavailability, limiting its clinical potential. In this study, we explored the use of TPGS-Soluplus micelles as an innovative drug delivery platform to enhance DAS solubility, stability, and therapeutic impact. A series of TPGS-Soluplus copolymers were synthesized, varying the D-α-tocopheryl polyethylene glycol succinate (TPGS) forms (1000, 2000, and 3500) and adjusting the TPGS to Soluplus weight ratios (1:1, 1:2, and 1:3). Our goal was to identify the optimal formulation with the highest entrapment efficiency, smallest particle size, and enhanced drug loading. The TPGS1000-Soluplus copolymer, with a DAS-to-polymer ratio of 1:30 and a TPGS ratio of 1:2, demonstrated superior performance, achieving an entrapment efficiency of 64.479 ± 1.45 % and drug loading of 5.05 ± 1.01 %. The DAS-loaded micelles (DAS-PMs) exhibited a notably small particle size of 64.479 ± 1.45 nm and demonstrated controlled release kinetics, with 85.60 ± 5.4 % of the drug released over 72 h.Cellular uptake studies using Hep G2 cells revealed significantly enhanced absorption of DAS-PMs compared to free DAS, reflected in lower IC50 values in MTT assays at 24 and 48 h. Pharmacokinetic analysis further highlighted the benefits of the DAS-PMs, with an AUC0-∞ 2.16 times higher and mean residual time (MRT) 1.3 times longer than free DAS, a statistically significant improvement (p

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Organic ammonium and phosphonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Particularly, quaternary ammonium lipids have demonstrated efficiency both as gene vectors and antibacterial agents. Here, aiming at finding new antibacterial devices belonging to both classes, we prepared a water-soluble quaternary ammonium lipid (6) and a phosphonium salt (1) by designing a synthetic path where 1 would be an intermediate to achieve 6. All synthesized compounds were characterized by Fourier-transform infrared spectroscopy and Nuclear Magnetic Resonance. Additionally, potentiometric titrations of NH3+ groups 1 and 6 were performed to further confirm their structure by determining their experimental molecular weight. The antibacterial activities of 1 and 6 were assessed first against a selection of multi-drug-resistant clinical isolates of both Gram-positive and Gram-negative species, observing remarkable antibacterial activity of both compounds against Gram-positive isolates of Enterococcus and Staphylococcus genus. Further investigations on a wider variety of strains of these species confirmed the remarkable antibacterial effects of 1 and 6 (MICs = 4–16 and 4–64 µg/mL, respectively), while 24 h-time-killing experiments carried out with 1 on different S. aureus isolates evidenced a bacteriostatic behavior. Moreover, both compounds 1 and 6, at the lower MIC concentration, did not show significant cytotoxic effects when exposed to HepG2 human hepatic cell lines, paving the way for their potential clinical application. [ABSTRACT FROM AUTHOR]

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior.

In the present work, we prepared coordination complexes of Co(III) glyoximate with the pyridine-based ligands. The reaction products of various [Co(gH/DmgH/dpg)2(L)(X)] with ligand L (L is pyridine (Py), 4-hydroxy pyridine (HP), 4-methyl pyridine (MP) and 4-(N,N-dimethyl) amino pyridine (DMAP) were synthesized. The compounds were studied by IR and NMR spectroscopy and thermal analysis. The spectroscopic results demonstrated that the proposed cobaloxime complexes are six coordinated species and octahedral geometry. Thermal stability of these complexes has been studied by thermogravimetric analysis (TGA) and reveals that the complexes are stable up to 350°C and follow a three-stage decomposition pattern depending upon the configuration that finally gives Co3O4 as a residue. The coordination compound was found to possess biological activity. The antimicrobial test results indicated that all the compounds have good antibacterial activity against various pathogens. Among all the complexes, nine complexes showed a good zone of inhibition and were subjected to cytotoxicity studies. Among them, only three complexes viz. [Co(gH)2(MP)Cl], [Co(gH)2(MP)Br] and [Co(dP)2(HP)I] showed good activity against human liver adenocarcinoma (HEP G2 cells). These complexes also confirmed the lowest concentration for IC50. [ABSTRACT FROM AUTHOR]

[Display omitted] The present study explores the synthesis of new potential Cereblon ligands, 2-amino derivatives of (thio)morpholine-3,5-diones. The resulting compounds demonstrate notable cytotoxic effects in tests conducted in vitro on myeloma cell lines, highlighting the potential of these compounds as molecular glues. [ABSTRACT FROM AUTHOR]

ABSTRACTThe emulsifying ability of SA01-OmpA (outer membrane protein A from Acinetobacter sp. SA01) was found to be constrained by challenges like low production efficiency and high costs associated with protein recovery from E. coli inclusion bodies, as described in our previous study. The present study sought to benefit from the advantages of the targeted truncating of SA01-OmpA protein, taking into account the reduced propensity of protein expression as inclusion bodies and cytotoxicity. Here, the structure and activity relationship of two truncated recombinant forms of SA01-OmpA protein was unraveled through a hybrid approach based on experimental data and computational methodologies, representing an innovative bioemulsifier with advantageous emulsifying activity. The recombinant truncated SA01-OmpA variants were cloned and heterologously expressed in E. coli host cells and subsequently purified. The results showed increased emulsifying activity of N-terminally truncated SA01-OmpA (NT-OmpA) compared to full-length SA01-OmpA. Molecular dynamics (MD) simulations analysis demonstrated a direct correlation between the C-terminally truncated SA01-OmpA (CT-OmpA) and its expression as inclusion bodies. Analysis of the structure-activity relationship of truncated variants of SA01-OmpA revealed that, compared to the full-length protein, deletion of the β-barrel portion from the N-terminal of SA01-OmpA increased the emulsifying activity of NT-OmpA while lowering its expression as inclusion bodies. Contrary to the full-length protein, the N-terminally truncated SA01-OmpA was not as cytotoxic, according to the MTT assay, FCM analysis, and AO/EB staining. The findings of this extensive study advance our knowledge of SA01-OmpA at the molecular level as well as the design and development of efficient bioemulsifiers.IMPORTANCEPrevious research (Shahryari et al. 2021, mSystems 6: e01175-20) introduced and characterized the SA01-OmpA protein as a multifaceted protein with a variety of functions, including maintaining cellular homeostasis under oxidative stress conditions, biofilm formation, outer membrane vesicles (OMV) biogenesis, and beneficial emulsifying capacity. By truncating the SA01-OmpA protein, the current study presents a unique method for developing protein-type bioemulsifiers. The findings indicate that the N-terminally truncated SA01-OmpA (NT-OmpA) has the potential to fully replace full-length SA01-OmpA as a novel bioemulsifier with significant emulsifying activity. This study opens up a new frontier in bioemulsifiers, shedding light on a possible relationship between the structure and activity of SA01-OmpA truncated forms.

Synthesis of substituted heterocyclic organic ligands and their metal complexes attract more attention in coordination chemistry in recent years owing to its interesting applications in pharmaceutical fields. In this research investigation, we designed a novel thio-substituted pyrazole ligand and synthesized its three novel Co(II), Ni(II), and Zn(II) metal complexes. The ligand, thio-substituted pyrazole is characterized by using single crystal x-ray diffraction data and various physico-chemical measurements such as elemental analysis and UV-Vis, IR, 13C, and 1H NMR, and HRMS spectral techniques. X-ray single crystal measurement of the substituted pyrazole was made on a Brucker AXS Kappa APEX II CCD diffractometer with graphite monochromatic MoK radiation. Metal complexes were characterized by various physico-chemical measurements such as elemental analysis, molar conductance, magnetic susceptibility data, and various spectral data supports. Based on the data obtained from those measurements, an octahedral geometry was assigned to all metal complexes. Furthermore, biological applications of the synthesized complexes were evaluated, mainly their cytotoxic, antitumour, and antimicrobial activities. Zn(II) complex has shown eminent cytotoxic ability, with an IC50 value of 46 μg/mL and its anticancer skill is scrutinized against "Ehrlich's Ascites Carcinoma" cell line-induced ascites tumour and "Dalton's Lymphoma Ascites" cell line-induced solid tumour in mice. Additionally, all the metal complexes showed promising antimicrobial skill against selected Gram-positive and Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Kamut sprouts (KaS) contain several biologically active compounds. In this study, solid-state fermentation using Saccharomyces cerevisiae and Latilactobacillus sakei was used to ferment KaS (fKaS-ex) for 6 days. The fKaS-ex showed a 26.3 mg/g dried weight (dw) and 46.88 mg/g dw of polyphenol and the β-glucan contents, respectively. In the Raw264.7 and HaCaT cell lines, the non-fermented KaS (nfKaS-ex) decreased cell viability from 85.3% to 62.1% at concentrations of 0.63 and 2.5 mg/mL, respectively. Similarly, the fKaS-ex decreased cell viability, but showed more than 100% even at 1.25 and 5.0 mg/mL concentrations, respectively. The anti-inflammatory effect of fKaS-ex also increased. At 600 µg/mL, the fKaS-ex exhibited a significantly higher ability to reduce cytotoxicity by suppressing COX-2 and IL-6 mRNA expressions as well as that for IL-1β mRNA. In summary, fKaS-ex exhibited significantly lower cytotoxicity and increased anti-oxidant and anti-inflammatory properties, indicating that fKaS-ex is beneficial for use in food and other industries. [ABSTRACT FROM AUTHOR]

Wild strawberry (Fragaria vesca L.) seed oil (WSO) recovered by two methods—cold pressing (CP) and extraction with supercritical carbon dioxide (SCO2E)—taking into account the different extraction times, was characterized for its composition and quality. The cytotoxicity assessment of WSOs was also carried out using the normal human dermal fibroblast (NHDF) cell line. Tocopherol and total polyphenol contents were significantly higher in WSO recovered by SCO2E, up to 1901.0 and 58.5 mg/kg, respectively, in comparison with CP oil. In CP oil, the highest content of carotenoids and squalene was determined (123.8 and 31.4 mg/kg, respectively). Phytosterol summed up to 5396 mg/kg in WSO collected in 30 min of SCO2E. Moreover, the highest oxidative stability was found for this oil. All studied WSOs were non-cytotoxic in lactate dehydrogenase (LDH) leaching and sulforhodamine B (SRB) assays; however, oils collected by SCO2E in 15 and 30 min were found to be cytotoxic in the tetrazolium salt (MTT) test, with the CC50 at a concentration of 3.4 and 5.5%, respectively. In conclusion, the composition of WSO indicates that, depending on the method of its recovery, seeds can have different bio-potencies and various applications. [ABSTRACT FROM AUTHOR]

Examining the critical role of anticoagulants in medical practice, particularly their central function in preventing abnormal blood clotting, is of the utmost importance. However, the study of interactions between blood proteins and alternative anticoagulant nano-surfaces is still understood poorly. In this study, novel approach involving direct functionalisation of magnetic iron oxide nanoparticles (MNPs) as carriers with sulphated dextran (s-dext) is presented, with the aim of evaluating the potential of magnetically-responsive MNPs@s-dext as anticoagulants. The physicochemical characterisation of the synthesised MNPs@s-dext includes crystal structure analysis, morphology study, surface and electrokinetic properties, thermogravimetric analysis and magnetic properties' evaluation, which confirms the successful preparation of the nanocomposite with sulfonate groups. The anticoagulant potential of MNPs@s-dext was investigated using a standardised activated partial thromboplastin time (APTT) test and a modified APTT test with a quartz crystal microbalance with dissipation (QCM-D) which confirmed the anticoagulant effect. Time-resolved solid-liquid interactions between the MNPs@s-dext and model blood proteins bovine serum albumin and fibrinogen were also investigated, to gain insight into their hemocompatibility, and revealed protein-repellence of MNPs@s-dext against blood proteins. The study also addressed comprehensive cytotoxicity studies of prepared nanocomposites, and provided valuable insights into potential applicability of MNPs@s-dext as a promising magnetic anticoagulant in biomedical contexts. [Display omitted] [ABSTRACT FROM AUTHOR]

Tannases are a family of esterases that catalyze the hydrolysis of ester and depside bonds of hydrolyzable tannins to release small compounds such as glucose. In this work, tannase production from Bacillus cereus strain KMS3-1 was purified and characterized. The standard methods, such as ammonium sulfate precipitation followed by gel filtration chromatography, were used to purify the enzyme tannase from KMS3-1. With 40% enzyme recovery, the purification process yielded a 1.93-fold increase in specific activity. Analysis using SDS-PAGE confirmed a molecular weight of about 40 kDa. Circular dichroism analysis revealed the secondary structure composition α-helix (12.03%), indicating a dominant role of β-turns (38.4%). A pH of 6.0 and a temperature between 50 and 60 °C were ideal for enzyme activity. Tannic acid has an enzyme K m value of 3.0 x 10−3 M and a V max of 4.45 U/mL. Surfactants, metal ions, organic solvents, and inhibitors significantly influence the enzyme activity. Cytotoxicity assays revealed the non-toxic nature of the purified enzyme on Vero cells and rat animal models. These results explore and contribute to a better understanding of tannase enzyme properties and their potential applications in the food and beverage industries. [ABSTRACT FROM AUTHOR]

Tridentate NNO donor Schiff base ligand and its mixed ligand zinc(II) complex were synthesized stoichiometrically and characterized by electronic, infrared, mass spectral techniques and elemental analysis. To understand the DNA binding ability, the complex was investigated by various analytical and spectroscopic techniques in presence of calf thymus DNA (CT‐DNA). The binding studies showed that the zinc complex interacts with DNA by groove binding mode with intrinsic binding strength of 2.11 × 105 M−1 and with bovine serum albumin the complex showed dynamic quenching attributed for changes in the secondary structure of BSA with efficient interaction. The MCF‐7 cell line studies of the zinc(II) complex with 90.8 μM IC50 value revealed that the complex is effective for the breast cancer cell line and has a potential as anticancer drug. Furthermore, the tridentate ligand and its mixed ligand zinc complex were screened for antibacterial and antifungal activities, which showed better antimicrobial activity for complex. [ABSTRACT FROM AUTHOR]

Herein, the synthesis and characterization of a novel composite biopolymer scaffold—based on equine type I collagen and hyaluronic acid—were described by using a reaction in heterogeneous phase. The resulting biomimetic structure was characterized in terms of chemical, physical, and cytotoxicity properties using human-derived lymphocytes and chondrocytes. Firstly, FT-IR data proved a successful reticulation of hyaluronic acid within collagen structure with the appearance of a new peak at a wavenumber of 1735 cm−1 associated with ester carbonyl stretch. TGA and DSC characterizations confirmed different thermal stability of cross-linked scaffolds while morphological analysis by scanning electron microscopy (SEM) suggested the presence of a highly porous structure with open and interconnected void areas suitable for hosting cells. The enzymatic degradation profile confirmed scaffold higher endurance with collagenase as compared with collagen alone. However, it was particularly interesting that the mechanical behavior of the composite scaffold showed an excellent shape memory, especially when it was hydrated, with an improved Young's modulus of 9.96 ± 0.53 kPa (p ≤ 0.001) as well as a maximum load at 97.36 ± 3.58 kPa compared to the simple collagen scaffold that had a modulus of 1.57 ± 0.08 kPa and a maximum load of 36.91 ± 0.24 kPa. Finally, in vitro cytotoxicity confirmed good product safety with human lymphocytes (viability of 81.92 ± 1.9 and 76.37 ± 1.2 after 24 and 48 h, respectively), whereas excellent gene expression profiles of chondrocytes with a significant upregulation of SOX9 and ACAN after 10 days of culture indicated our scaffold's ability of preserving chondrogenic phenotype. The described material could be considered a potential tool to be implanted in patients with cartilage defects. [ABSTRACT FROM AUTHOR]

In the current study, the fruits of a popular ornamental tree, Sorbus intermedia, were investigated phytochemically and biologically as potential source of bioactive triterpenes. Six terpenoids were isolated and examined with respect to their cytotoxic activity using a broad screening in vitro model and multivariate analysis for better demonstration of the effects on cancer cells. This chemometric approach allowed us to confirm that the structural characteristics of the compounds significantly affected their impact on cell lines. Ursolic acid was found to be the most potent cytotoxic agent with IC50 predominantly

In this work, we report the synthesis and characterization of a mono-nuclear "two wall" aryl-extended calix[4]pyrrole receptor (2Au) decorated with an acetylide-gold(I)-PTA complex at its upper rim. We describe the 1H NMR titration experiments of 2Au and its "two wall" aryl-extended calix[4]pyrrole synthetic precursors: the non-symmetric mono-iodo-mono-ethynyl 2 and the symmetric bis-iodo 3 with TBACl in dichloromethane and acetone solution. In acetone solution, we use isothermal titration calorimetry (ITC) experiments to thermodynamically characterize the formed 1:1 chloride complexes and perform pair-wise competitive binding experiments. In both solvents, we measured a decrease in the binding constant of the mono-nuclear 2Au complex for chloride compared to the parent mono-iodo-mono-ethynyl 2. In turn, receptor 2 also shows a reduction in binding affinity for chloride compared to its precursor bis-iodo calix[4]pyrrole 3. The free energy differences (∆G) of the 1:1 chloride complexes cannot be exclusively attributed to their dissimilar electrostatic surface potential values either at the center of the meso-phenyl wall or its para-substituent. We conclude that solvation/desolvation processes play an important role in the stabilization of the chloride complexes. In acetone solution and in the presence of TBACl, 6Au, a reference compound for the acetylide Au(I)•PTA unit, produces a bis(alkynyl)gold(I) anionic complex [7Au]−. Thus, the observation of two separate sets of signals for the bound aromatic calix[4]pyrrole protons, when more than 1 equiv. of the salt is added, is assigned to the formation of the chloride complexes of 2Au and of the "in situ" formed calix[4]pyrrole anionic dimer [8Au]−. Finally, preliminary data obtained in cell viability assays of 2Au and 6Au with human cancer cells lines assign them with moderate activities showing that the calix[4]pyrrole unit is not relevant. [ABSTRACT FROM AUTHOR]

and its derivatives are an important class of heterocyclic compounds that possess a wide range of therapeutic and pharmacological properties, while thiourea is an organosulphur compound in that it resembles urea except that the atom oxygen has been replaced by a Sulphur atom, but the properties of urea and thiourea are significantly different. The current work concerns the synthesis of a new class of urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates in the presence of trimethylamine. The IR and NMR spectral data were performed for the urea and thiourea derivatives of the compounds [(3c & 3f) & (3d & 3e)], respectively. Molecular docking studies of the compounds (3a-h) revealed the binding mode involved in the active site of DNA gyrase. The synthesized urea and thiourea derivatives of isoniazid with various isocyanates and isothiocyanates were tested for their antibacterial activity against gram-positive and gram-negative bacteria using the "disc diffusion method". Of all compounds tested, the urea derivatives (3a &3d), the thiourea derivatives (3e & 3g) showed more potent activity than the other compounds. The MTT assay revealed concentration dependent cytotoxic effects over a concentration range 25-200 µg/mL. [ABSTRACT FROM AUTHOR]

The study focused on fabricating and characterizing sorafenib-loaded calcium alginate beads for potential cancer therapy application. The beads were synthesized via ionotropic gelation using calcium chloride as a crosslinker. Successful sorafenib encapsulation was confirmed through various analytical techniques, including FTIR, XRD, SEM, and UV-Vis spectroscopy. FTIR analysis showed shifts in characteristic bands, indicating effective drug loading. XRD patterns revealed both amorphous and crystalline characteristics, with peaks corresponding to the drug and polymer. SEM images depicted spherical beads with surface roughness. UV-Vis spectrum analysis demonstrated high encapsulation efficiencies ranging from 99.48 % to 99.82 %, depending on the sorafenib concentration. Biodegradation studies suggested the beads' potential for drug delivery, showing gradual weight and shape loss. Antioxidant assays indicated superior scavenging activity, while antibacterial assays showed good activity against Bacillus species. Cytotoxicity studies revealed specific toxicity against MCF7 breast cancer cells. Drug release data fitted well with the first-order model, indicating controlled release properties. These findings highlight the potential of sorafenib-loaded calcium alginate beads as an effective delivery system for cancer therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Kamut sprouts (KaS) contain several biologically active compounds. In this study, solid-state fermentation using Saccharomyces cerevisiae and Latilactobacillus sakei was used to ferment KaS (fKaS-ex) for 6 days. The fKaS-ex showed a 26.3 mg/g dried weight (dw) and 46.88 mg/g dw of polyphenol and the β-glucan contents, respectively. In the Raw264.7 and HaCaT cell lines, the non-fermented KaS (nfKaS-ex) decreased cell viability from 85.3% to 62.1% at concentrations of 0.63 and 2.5 mg/mL, respectively. Similarly, the fKaS-ex decreased cell viability, but showed more than 100% even at 1.25 and 5.0 mg/mL concentrations, respectively. The anti-inflammatory effect of fKaS-ex also increased. At 600 µg/mL, the fKaS-ex exhibited a significantly higher ability to reduce cytotoxicity by suppressing COX-2 and IL-6 mRNA expressions as well as that for IL-1β mRNA. In summary, fKaS-ex exhibited significantly lower cytotoxicity and increased anti-oxidant and anti-inflammatory properties, indicating that fKaS-ex is beneficial for use in food and other industries.

Fluorescein and phenolphthalein derivatives have been synthesized and screened for their bioactivity via molecular docking, cytotoxicity and antioxidant studies. In molecular docking studies, the compounds 3d have exhibited better glide score and hydrogen bonding ability when docked with t-RNA Dimethylallyltransferase. Antioxidant capabilities were evaluated via DPPH and ABTS radical scavenging activity. In this screening, compound 3d exhibited better inhibition efficiency in the DPPH and ABTS methods. Cytotoxicity of the compounds was assessed by the cell sustainability assay against human cervical cancer cell line (HeLa). All the synthesized compounds exhibited cytotoxic effects against HeLa cells and compounds 3d displayed better activity (IC50) than the standard drug (doxorubicin). [ABSTRACT FROM AUTHOR]

Tranistion metals [Co, Ni, and Cu] complexes of pyridine-thiophene derivative ligand 2-((E)-2-((5-methylthiophen-2-yl) methylene)hydrazinyl)-4-methyl-6-phenylpyridine-3-carbonitrile(MTHPC) have been synthesized and characterized with different spectral investigations viz. UV-Vis, FT-IR, 1H-NMR, and ESR. The ligand and metal complexes were screened for in-vitro cytotoxicity studies against two carcinoma cell lines A549 (Lung carcinoma cells) and HepG2 (Hepatocellular carcinoma cell). The results were found to possess cytotoxic effect. Nickel complex had shown high potent cytotoxic effect for A549 cell lines and Copper complex shown high cytotoxic effect for HepG2 cell lines. The ligand and metal complexes were tested in vitro against Gram -ve bacteria such Pseudomonas desmolyticum, Escherichia coli, and Klebsiella aerogenes, as well as Gram +ve bacteria like Staphylococcus aureus. Copper and Cobalt complex has modest antibacterial action at increasing concentrations, but Nickel complex has significant antibacterial activity. [ABSTRACT FROM AUTHOR]

This contribution of work describes the synthesis of a novel mixed Schiff base ligand, 3-((2-((1-(2-hydroxyphenyl)ethylidene)amino)ethyl)imino)-N-(o-tolyl)butanamide derived from 1,2-ethylenediamine, o-hydroxyacetophenone and 2-methylacetoacetanilide and its some transition metal, Mn(II), Fe(III), Co(II), Ni(II) and Cu(II) complexes. The multidentate Schiff base ligand was characterized analytically by elemental analysis and spectroscopically by HRMS, IR-, 1H NMR, 13C NMR- and UV-Vis spectral data in addition to the above, physico-chemical methods like elemental analysis, molar conductance, magnetic susceptibility measurement and various spectral techniques were employed for the characterization of the metal complexes. This study investigated that, the potential applications of metal complexes as cytotoxicity and, in vivo antitumor efficiency against Earlich Ascites Carcinoma cell induced ascites tumor and Dalton’s Lymphoma Ascites cell induced solid tumor in Swiss Albino female mice. Antioxidant radical scavenging activity of complexes have bee evaluated against DPPH, super oxide anion, nitric oxide and H2O2 radicals. Antimicrobial screening by MIC method also performed some selected microbes. The present study proposed that the ligand and its metal complexes behave as potential cytotoxic, anticancer, antioxidant and antibacterial and antifungal agents.

[Display omitted] • Synthesis of N (4) heterocyclic substituted thiosemicarbazones and thiadiazoles. • DNA/BSA binding assays using absorption and emission spectroscopy. • Through molecular docking and dynamics studies, the ligands' ability to bind BSA were tested. • Drug-likeness (Swiss-ADME) and electronic structural characteristics (DFT) of TSL1–TSL4 were predicted. • Evaluation of cytotoxicity of TSL1-TSL4 against the A459, MCF7, HepG-2 cancer cells and normal Vero cells. Cancer's global impact necessitates innovative and less toxic treatments. Thiosemicarbazones (TSCs), adaptable metal chelators, offer such potential. In this study, we have synthesized N (4)-substituted heterocyclic TSCs from syringaldehyde (TSL1 , TSL2), and also report the unexpected copper-mediated cyclization of the TSCs to form thiadiazoles (TSL3 , TSL4), expanding research avenues. This work includes extensive characterization and studies such as DNA/protein binding, molecular docking, and theoretical analyses to demonstrate the potential of the as-prepared TSCs and thiadiazoles against different cancer cells. The DFT results depict that the thiadiazoles exhibit greater structural stability and reduced reactivity compared to the corresponding TSCs. The docking results suggest superior EGFR inhibition for TSL3 with a binding constant value of − 6.99 Kcal/mol. According to molecular dynamics studies, the TSL3 -EGFR complex exhibits a lower average RMSD (1.39 nm) as compared to the TSL1 -EGFR complex (3.29 nm) suggesting that both the thiadiazole and thiosemicarbazone examined here can be good inhibitors of EGFR protein, also that TSL3 can inhibit EGFR better than TSL1. ADME analysis indicates drug-likeness and oral availability of the thiadiazole-based drugs. The DNA binding experiment through absorption and emission spectroscopy discovered that TSL3 is more active towards DNA which is quantitatively calculated with a K b value of 4.74 × 106 M−1, K q value of 4.04 × 104 M−1and K app value of 5 × 106 M−1. Furthermore, the BSA binding studies carried out with fluorescence spectroscopy showed that TSL3 shows better binding capacity (1.64 × 105 M−1) with BSA protein. All the compounds show significant cytotoxicity against A459-lung, MCF-7-breast, and HepG2-liver cancer cell lines; TSL3 exhibits the best cytotoxicity, albeit less effective than cisplatin. Thiadiazoles demonstrate greater cytotoxicity than the TSCs. Overall, the promise of TSCs and thiadiazoles in cancer research is highlighted by this study. Furthermore, it unveils unexpected copper-mediated cyclization of the TSCs to thiadiazoles. [ABSTRACT FROM AUTHOR]

• The eight new Schiff bases have been prepared and elucidated with spectroscopic approaches. • Antimicrobial activities of all synthesized compounds have been determined. • Compounds-pUC18 plasmid DNA interaction have been investigated by gel electrophoresis. • The cytotoxic activities of the compounds have been determined on the HT-29 cell line. • The nucleophilic/electrophilic attack abilities and antibacterial/cytotoxic activities were investigated by DFT calculations. New Schiff bases (1–8) have been prepared from numerous aldehydes and thio/carbohydrazide. The chemical structures of these compounds were characterized using IR, 1H NMR, 13C NMR spectroscopic methods, and elemental analysis. Electronic and spectroscopic properties of the compounds were determined by DFT calculations performed at the B3LYP/6–311++ G (2d,2p) level of theory and were analyzed comparatively with experimental findings. The relationship between some global reactivity parameters and the nucleophilic-electrophilic attack abilities of the compounds and their antimicrobial and cytotoxic activities was also investigated. The antimicrobial effects of the synthesized compounds on microorganisms were screened using disc diffusion methods. According to the disc diffusion results, compound 8 in particular exhibits a high antibacterial potential against Bacillus cereus (15.66 ± 0.57 mm). The interaction of synthesized compounds with pUC18 plasmid DNA was analyzed by the agarose gel electrophoresis method. The results showed that compounds 6, 7 , and 8 interact with plasmid DNA and cause fragmentation of the Form I structure. In addition, in vitro , the cytotoxic activity of compounds on HT-29 (human adenocarcinoma colon) cell lines was investigated by the MTT method. Our study showed that compounds 7 and 8 have cytotoxic effects on HT-29 cell lines. The IC 50 value was determined to be 96.93 µM for compound 7 and 91.55 µM for compound 8. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • This work describes the surface functionalization of ZnO nanoparticles with 2-oxo-2H-chromene-3-carboxylic acid (3-CCA) coupled beta-cyclodextrin (β-CD) as a biocompatible system (ZnO-β-CD-3-CCA) and the evaluation of its antimicrobial and anticancer properties. • The study confirmed the antimicrobial characteristics of both ZnO NPs and ZnO-β-CD-3-CCA system against microbial strains, such as Streptococcus haemolyticus , Bacillus cereus , Salmonella paratyphi, Salmonella typhimurium , and Conidiobolus coronatus. • The cytotoxic effect of both ZnO NPs and ZnO-β-CD-3-CCA system were specific to MCF-7 and Hep G2 cancer cells in a dose-dependent manner, with minimal impact on normal rat spleen cells. • Compared to ZnO nanoparticles, the surface-functionalized ZnO NPs exhibit increased antimicrobial activity and in vitro cytotoxicity, suggesting potential uses in medical therapies. Nanomedicine has newly emerged as a superior alternative for the treatment of numerous life-threatening illnesses. Zinc oxide nanomaterials have attracted a lot of attention in this decade because of their enormous potential in a wide range of biomedical applications. This work describes the surface functionalization of zinc oxide nanoparticles (ZnO NPs) with 2-oxo-2H-chromene-3-carboxylic acid (3-CCA) coupled beta-cyclodextrin (β-CD) to create a biocompatible system (ZnO-β-CD-3-CCA) and the evaluation of its antimicrobial and anticancer properties. Different characterization techniques, such as X-ray powder diffraction, UV–Vis spectroscopy, FTIR, transmission, and scanning electron microscopy, were used to characterize the biocompatible system. The antimicrobial properties of the synthesized ZnO NPs and the surface functionalized ZnO-β-CD-3-CCA system were evaluated using the disc diffusion method. Modification with functionalized β-CD systems increased the bacteriostatic effect of ZnO nanoparticles against various microbes. In vitro cytotoxicity of ZnO NPs and surface functionalized ZnO-β-CD-3-CCA system was evaluated against two distinct cancer cell lines: MCF-7, Hep G2, and normal rat spleen cells employing MTT assay, and the results highlight that the selective cytotoxicity of the surface functionalized ZnO-β-CD-3-CCA system against the human breast cancer (MCF-7) and human liver cancer (Hep G2) cell lines were superior to that of ZnO NPs. Also, the developed systems were less toxic to normal rat spleen cells. This work is significant because it could result in next-generation nanoparticle-based cancer treatments that are more successful. [ABSTRACT FROM AUTHOR]

Materials currently used for vascular grafts are characterized by limited biocompatibility. Especially challenging is obtaining the degradable graft to regenerate a patient's native tissue. Poly(alkylene citrates) (PACs) are promising for soft tissue engineering applications; however, their degradation must follow a specific profile and must not result in the formation of any substances cytotoxic to the human body. The aim of this study was to evaluate the processes that occur throughout the hydrolytic degradation of PACs with a 2:3 M ratio of citric acid and diol, additionally modified with an antioxidant compound: glutathione (GSH). The samples were tested after various time intervals of incubation in an aqueous environment (up to 3 months), taking into account the influence of the type of diol used (1,6-hexanediol or 1,8-octanediol), the time of polymer cross-linking (4 or 10 days) and the presence of a different amount of GSH (0.4 or 0.8 wt%). Structural changes in the samples were monitored by means of swelling capacity, mass changes, hardness tests, mass spectrometry, and UV spectrofluorimetry. After 3 months of degradation, a higher weight loss was observed for the samples based on 1,6-hexanediol (>20 wt%) than those based on 1,8-octanediol (6–16 wt%). Based on the values obtained, the approximate time of 80% of the mass loss was calculated, which was higher for samples cross-linked for 10 days than 4 days. The samples based on 1,8-octanediol degraded slower than those of 1,6-hexanediol, but their degradation pattern was more linear and the amount of heavy ions present in the supernatant was negligible. In vitro studies on L929 fibroblasts did not show a cytotoxic effect of the materials tested. The study proved that GSH does not cause significant changes in the degradation profiles, sufficiently providing the fluorescence properties of the materials. Furthermore, any drastic changes in the material for up to 3 weeks followed by progressive degradation may support the tissue before the regeneration process begins. [Display omitted] • Citric acid and 1,6-hexanediol or 1,8-octanediol polyesters modified with glutathione. • Polyesters degradation occurs as a result of small fragments detachment from the polymer chains. • Degradation kinetics depends on diol type, but not glutathione modification. • Studied materials not cytotoxic with fibroblasts. [ABSTRACT FROM AUTHOR]

In this work, we report the synthesis and characterization of a mono-nuclear “two wall” aryl-extended calix[4]pyrrole receptor (2Au) decorated with an acetylide-gold(I)-PTA complex at its upper rim. We describe the 1H NMR titration experiments of 2Au and its “two wall” aryl-extended calix[4]pyrrole synthetic precursors: the non-symmetric mono-iodo-mono-ethynyl 2 and the symmetric bis-iodo 3 with TBACl in dichloromethane and acetone solution. In acetone solution, we use isothermal titration calorimetry (ITC) experiments to thermodynamically characterize the formed 1:1 chloride complexes and perform pair-wise competitive binding experiments. In both solvents, we measured a decrease in the binding constant of the mono-nuclear 2Au complex for chloride compared to the parent mono-iodo-mono-ethynyl 2. In turn, receptor 2 also shows a reduction in binding affinity for chloride compared to its precursor bis-iodo calix[4]pyrrole 3. The free energy differences (∆G) of the 1:1 chloride complexes cannot be exclusively attributed to their dissimilar electrostatic surface potential values either at the center of the meso-phenyl wall or its para-substituent. We conclude that solvation/desolvation processes play an important role in the stabilization of the chloride complexes. In acetone solution and in the presence of TBACl, 6Au, a reference compound for the acetylide Au(I)•PTA unit, produces a bis(alkynyl)gold(I) anionic complex [7Au]−. Thus, the observation of two separate sets of signals for the bound aromatic calix[4]pyrrole protons, when more than 1 equiv. of the salt is added, is assigned to the formation of the chloride complexes of 2Au and of the “in situ” formed calix[4]pyrrole anionic dimer [8Au]−. Finally, preliminary data obtained in cell viability assays of 2Au and 6Au with human cancer cells lines assign them with moderate activities showing that the calix[4]pyrrole unit is not relevant.

A polydentate Schiff base ligand, L was synthesized via condensation reaction between o -vanillin (OVan) and trimethyl- m -phenylenediamine [(Me)MPD]. Its Cu(II), Ni(II), and Zn(II) dinuclear complexes were prepared through complexation with corresponding acetate salts. The compounds were characterized via CHN elemental analyzer, molar conductivity, magnetic susceptibility, TGA, IR, 1H and 13C NMR. The crystal structure of the ligand, L and zinc(II) complex, Zn2L2 were elucidated by using single crystal x-ray diffraction. The crystal structure of Zn2L2 showed that the two Zn(II) metal atoms serve as bridges between the two units of the ligand through ONNO donor atoms leading to the formation of a centrosymmetric cyclic dinuclear complex. Based on the single x-ray crystallography, the zinc atoms exhibit a distorted tetrahedral geometry. Hirshfeld surface analysis was performed to determine the intermolecular interactions in the crystal structures. From this analysis, it revealed that H···H interaction for L (55%) and Zn2L2 (62.7%) was the dominant intermolecular interaction in the total area of Hirshfeld surface. The ν(C N) and ν(C O) peaks in IR spectra of the ligand L appeared at 1615 cm−1 and 1255 cm−1, respectively. The peaks shifted to lower and higher frequency by Δν of 4–12 cm−1 in the complexes. The new peaks assignable to ν(M N) and ν(M O) were observed at 514–562 cm−1 and 422–436 cm−1, respectively, indicating the coordination of the metal centers to the azomethine N and phenolic O. The Cu(II) and Ni(II) complexes are paramagnetic with μ eff of 1.90 and 2.89 B.M., respectively. The thermal gravimetric analysis revealed the presence of three lattice water molecules in Cu(II) complex. The cytotoxicity studies of all compounds were carried out against colon cancer cell lines (HCT116). The parent ligand was found to be less cytotoxic than its metal complexes. Cu(II) showed the highest activity with IC 50 of 0.73 ± 0.21 μM, better than the standard 5-FU. [Display omitted] [ABSTRACT FROM AUTHOR]

Methyl-substituted 8-hydroxyquinolines (Hquin) were successfully used to synthetize five-coordinated oxovanadium(IV) complexes: [VO(2,6-(Me)2-quin)2] (1), [VO(2,5-(Me)2-quin)2] (2) and [VO(2-Me-quin)2] (3). Complexes 1–3 demonstrated high catalytic activity in the oxidation of hydrocarbons with H2O2 in acetonitrile at 50 °C, in the presence of 2-pyrazinecarboxylic acid (PCA) as a cocatalyst. The maximum yield of cyclohexane oxidation products attained was 48%, which is high in the case of the oxidation of saturated hydrocarbons. The reaction leads to the formation of a mixture of cyclohexyl hydroperoxide, cyclohexanol and cyclohexanone. When triphenylphosphine is added, cyclohexyl hydroperoxide is completely converted to cyclohexanol. Consideration of the regio- and bond-selectivity in the oxidation of n-heptane and methylcyclohexane, respectively, indicates that the oxidation proceeds with the participation of free hydroxyl radicals. The complexes show moderate activity in the oxidation of alcohols. Complexes 1 and 2 reduce the viability of colorectal (HCT116) and ovarian (A2780) carcinoma cell lines and of normal dermal fibroblasts without showing a specific selectivity for cancer cell lines. Complex 3 on the other hand, shows a higher cytotoxicity in a colorectal carcinoma cell line (HCT116), a lower cytotoxicity towards normal dermal fibroblasts and no effect in an ovarian carcinoma cell line (order of magnitude HCT116 > fibroblasts > A2780).

Ridhima Juneja, Indrajit Roy Department of Chemistry, University of Delhi, New Delhi, Delhi, India Abstract: Magnetism has wide applications in various fields, such as diagnostics, drug targeting, molecular biology, cell isolation, cell purification, hyperthermia, and radioimmunoassay. In this study, we synthesized niosomes doped with iron oxide nanoparticles and a fluorophore for potential applications in magnetically targeted drug delivery. Release kinetics of the fluorophore and cytotoxicity were assessed. The results demonstrate that niosomes doped with iron oxide nanoparticles can serve as proficient and effective drug carriers in magnetically targeted drug delivery. Keywords: iron oxide nanoparticles, niosomes, fluorophores, drug carriers, magnetically targeted delivery

The emulsifying ability of SA01-OmpA (outer membrane protein A from Acinetobacter sp. SA01) was found to be constrained by challenges like low production efficiency and high costs associated with protein recovery from E. coli inclusion bodies, as described in our previous study. The present study sought to benefit from the advantages of the targeted truncating of SA01-OmpA protein, taking into account the reduced propensity of protein expression as inclusion bodies and cytotoxicity. Here, the structure and activity relationship of two truncated recombinant forms of SA01-OmpA protein was unraveled through a hybrid approach based on experimental data and computational methodologies, representing an innovative bioemulsifier with advantageous emulsifying activity. The recombinant truncated SA01-OmpA variants were cloned and heterologously expressed in E. coli host cells and subsequently purified. The results showed increased emulsifying activity of N-terminally truncated SA01-OmpA (NT-OmpA) compared to full-length SA01-OmpA. Molecular dynamics (MD) simulations analysis demonstrated a direct correlation between the C-terminally truncated SA01-OmpA (CT-OmpA) and its expression as inclusion bodies. Analysis of the structure-activity relationship of truncated variants of SA01-OmpA revealed that, compared to the full-length protein, deletion of the β-barrel portion from the N-terminal of SA01-OmpA increased the emulsifying activity of NT-OmpA while lowering its expression as inclusion bodies. Contrary to the full-length protein, the N-terminally truncated SA01-OmpA was not as cytotoxic, according to the MTT assay, FCM analysis, and AO/EB staining. The findings of this extensive study advance our knowledge of SA01-OmpA at the molecular level as well as the design and development of efficient bioemulsifiers.IMPORTANCEPrevious research (Shahryari et al. 2021, mSystems 6: e01175-20) introduced and characterized the SA01-OmpA protein as a multifaceted protein with a variety of functions, including maintaining cellular homeostasis under oxidative stress conditions, biofilm formation, outer membrane vesicles (OMV) biogenesis, and beneficial emulsifying capacity. By truncating the SA01-OmpA protein, the current study presents a unique method for developing protein-type bioemulsifiers. The findings indicate that the N-terminally truncated SA01-OmpA (NT-OmpA) has the potential to fully replace full-length SA01-OmpA as a novel bioemulsifier with significant emulsifying activity. This study opens up a new frontier in bioemulsifiers, shedding light on a possible relationship between the structure and activity of SA01-OmpA truncated forms., Competing Interests: The authors declare no conflict of interest.

Binding interaction of two copper complexes with DNA and bovine serum albumin has been investigated and supported by using molecular docking tool. One complex shows a higher binding affinity exhibiting in vitro moderate growth suppression activity against human breast (MCF7) cancer cell line (= 24 ± 6.24 μM). Two Schiff bases HL and HL′, having potential tridentate O,N,N′ donor sets, have been used for the synthesis of two copper(II) complexes, namely [Cu(HL)(pdc)] 2 (1) and [Cu(L′) 2 ] 2 (2′), where HL = 2-([2-(piperazin-yl)ethylimino]methyl)phenol, pdc = py-2,5-dicarboxylate and HL′ = 2-(((2-(di-isopropylamino)ethyl)imino)methyl)phenol. X-ray single crystal analysis of complex 1 shows a centro-symmetric dimer. It crystallizes with a number of lattice water molecules that form a network of H-bonds, also involving the protonated piperazinium fragment, giving rise to a 3D supramolecular architecture. Complex 2′ also crystallizes as dinuclear, formed through mutual bridging phenol oxygen atoms as [Cu(L′) 2 ] 2 , whilst an ESI mass spectrometry study evidences that in solution the complex exists as mononuclear [Cu(L′) 2 ] (2). The interaction of complexes 1 and 2 with calf thymus DNA (CT-DNA) and with bovine serum albumin (BSA) was investigated using electronic absorption and fluorescence spectroscopic techniques. In both studies the results show a higher binding affinity of complex 1 in comparison to 2. The anticancer activity of the complexes against human breast (MCF7) cancer cell lines reveals that complex 1 has moderate growth suppression activity against these cells with an IC 50 value of 24 ± 6.24 μM. [ABSTRACT FROM AUTHOR]

A library of novel 1,3,4-oxadiazole substituted imidazo[1,2-a]pyridine based molecular hybrids have been synthesized and evaluated against Mycobacterium tuberculosis H37Rv. Out of 59 compounds synthesized, ten compounds show activity in the range of 3.125-12.5 μM. Compound 8p is found to be most active with MIC99 value of 3.125-6.25 μM. Further, these ten compounds have also been tested for their toxicity against THP-1 cell line and are found to be non-toxic with TC50 value in the range of (10 - >50 μM) concentration. [ABSTRACT FROM AUTHOR]

A series of heterocyclic compounds were synthesized and fully characterized. The geometry optimization was carried out using the Density Functional Theory (DFT) method and the electronic properties of 1‐(2‐hydroxyethyl)‐3‐(2‐(piperidinium‐1‐yl)ethyl chloride)‐1H‐benzo[d]imidazol‐3‐ium bromide and 1‐(2‐methylbenzyl)‐3‐(2‐(piperidinium‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium dichloride were calculated. Furthermore, the all compounds were evaluated for their potential anticancer activity towards different human cell lines. While 1‐(naphthalen‐1‐ylmethyl)‐3‐(2‐(piperidin‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium chloride possessing naphthalen‐1‐ylmethyl group as substituent demonstrated important cytotoxic activity against human colorectal adenocarcinoma epithelial colon cell line (DLD‐1) with an IC50 value of 15.56 ± 4.01 μM, compound containing 4‐methylbenzyl group showed the most anticancer activity towards human liver epithelial hepatocellular carcinoma cell line (HepG2) with IC50 value of 15.16 μM. Moreover, microscopic examination of cells was done using Leica inverted microscopy and Olympus confocal microscope. Confocal images of DLD‐1 and human normal epithelial virus transformed cell line (Beas‐2B), which were treated with 20 μM of compounds, indicated that compounds 1‐(4‐methylbenzyl)‐3‐(2‐(piperidinium‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium dichloride and 1‐(naphthalen‐1‐ylmethyl)‐3‐(2‐(piperidin‐1‐yl)ethyl)‐1H‐benzo[d]imidazol‐3‐ium chloride had more cytotoxic activity. [ABSTRACT FROM AUTHOR]

In search for antitumor metal-based drugs that would mitigate the severe side-effects of cisplatin, Ru(II) complexes are gaining increasing recent interest. In this work, we report on the synthesis, characterization (1H- and 13C-NMR, FT-IR), and cytotoxicity studies of two new half-sandwich organometallic Ru(II) complexes of the general formula [Ru(η6-arene)(XY)Cl](PF6) where arene = benzene or toluene and XY = bidentates: dipyrido[3,2-a:2′,3′-c]phenazine (dppz) or 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip), which are bound to Ru(II) via two phenanthroline-N atoms in a characteristic "piano-stool" configuration of Ru(II)-arene complexes—as confirmed by vibrational and NMR spectra. In addition, cytotoxic studies were performed for similar half-sandwich organometallic [Ru(η6-p-cymene)(Me2dppz)Cl]PF6 complex (Me2dppz = 11,12-dimethyl-dipyrido[3,2-a:2′,3′-c]phenazine). This study is complemented with elaborate modeling with density functional theory (DFT) calculations, which provided insight into reactive sites of Ru(II) structures, further detailed by molecular docking on the B-DNA dodecamer, which identified binding sites and affinities: most pronounced for the [Ru(η6-benzene)(aip)Cl](PF6) in both A-T and G-C regions of the DNA minor groove. Cytotoxic activity was probed versus tumor cell lines B16, C6, and U251 (B16 mouse melanoma, C6 rat glioma, U251 human glioblastoma) and non-tumor cell line HACAT (HACAT normal human keratinocytes). [ABSTRACT FROM AUTHOR]

Graphical abstract A series of trichlorogermyl complexes of the type [η6-(Arene)Ru(PR 3)Cl(GeCl 3)], including full spectroscopic characterisation are reported and their cytotoxicity towards A2780 or HEK293 cell lines are also reported along with DFT studies. Abstract The synthesis of five half sandwich ruthenium(II) trichlorogermyl complexes of the type [(η6-Arene)Ru(PR 3)Cl(GeCl 3)] (PR 3 = Phosphane and phosphite ligands; Arene = p -cymene or C 6 H 5 -OC 2 H 4 OH) is reported: [(η6- p -cymene)Ru(P(OMe) 3)Cl(GeCl 3)] (1), [(η6- p -cymene)Ru(P(OPh) 3)Cl(GeCl 3)] (2), [(η6- p -cymene)Ru(PPh 3)Cl(GeCl 3)] (3), [(η6- p -cymene)Ru(pta)Cl(GeCl 3)] (pta = 1,3,5-triaza-7-phosphaadamantane) (4) and [(η6-C 6 H 5 -OC 2 H 4 OH)Ru(pta)Cl(GeCl 3)] (5). The nature of the η6-arene and phosphane ligand was varied and the complexes have been prepared by facile insertion of GeCl 2 (from GeCl 2 .(dioxane)) into the Ru-Cl bonds of the respective easily accessible precursor complexes [(η6-Arene)Ru(PR 3)Cl 2 ]. The complexes were fully spectroscopically characterized by 1H, 13C{1H} and 31P{1H} NMR spectroscopy, UV-Vis, ATR-IR, HRMS (ESI) and their thermal behavior elucidated by TGA. Their cytotoxicity to human ovarian carcinoma (A2780) and non-tumorigenic human embryonic kidney HEK293 cell lines is also reported, and represents the first cytotoxic investigations of Ru(II) germyl complexes to date. The first DFT studies (B3LYP; basis set 6-31+G(d,p) for H, C, O, P, Cl, N, and Ge atoms and DGDZVP for Ru atom) on trichlorogermyl ruthenium complexes were carried out on complex 2 and 5 in order to gain insights into the bonding situation between Ru and Ge and are reported. [ABSTRACT FROM AUTHOR]

This work presents a new look at the application of cyclodextrins (CD) as a drug nanocarrier. Two different cyclodextrins (αCD, βCD) were covalently conjugated to branched polyethylenimine (PEI), which was additionally functionalized with folic acid (PEI-βCD-αCD-FA). Here, we demonstrated that the combination of αCD and βCD enabled to load and control release of two anticancer drugs: doxorubicin (DOX) and beta-lapachone (beta-LP) (DOX in β-CD and beta-LP into α-CD) via host-guest inclusion. The PEI-βCD(DOX)-αCD-FA nanoconjugate was used to transport anticancer drugs into A549 lung cancer cells for estimation the cytotoxic and antitumor effect of this nanoconjugate. The presence of FA molecules should facilitate the penetration of studied nanoconjugate into the cell. Whereas, the non-cellular experiments proved that the drugs are released from the carrier mainly in the pH 4.0. The release mechanism is found to be anomalous in all studied cases.

The ionic gelation technique allows us to obtain nanoparticles able to function as carriers for hydrophobic anticancer drugs, such as 5-fluoruracil (5-FU). In this study, reticulated chitosan– docosahexaenoic acid (Chi–DHAr) nanoparticles were synthesized by using a chemical reaction between amine groups of chitosan (Chi) and carboxylic acids of docosahexaenoic acid (DHA) and the presence of a link between Chi and DHA was confirmed by FT-IR, while the size and morphology of the obtained Chi-DHAr nanoparticles was evaluated with dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. Drug-loading content (DLC) and drug-loading efficiency (DLE) of 5-FU in Chi-DHAr nanoparticles were 33.74 ± 0.19% and 7.9 ± 0.26%, respectively, while in the non-functionalized nanoparticles (Chir + 5FU), DLC, and DLE were in the ranges of 23.73 ± 0.14%, 5.62%, and 0.23%, respectively. The in vitro release profile, performed in phosphate buffer saline (PBS, pH 7.4) at 37 °C, indicated that the synthetized Chi–DHAr nanoparticles provided a sustained release of 5-FU. Based on the obtained regression coefficient value (R2), the first order kinetic model provided the best fit for both Chir and Chi-DHAr nanoparticles. Finally, cytotoxicity studies of chitosan, 5-FU, Chir, Chir + 5-FU, Chi-DHAr, and Chi-DHAr + 5-FU nanoparticles were conducted. Overall, Chi-DHAr nanoparticles proved to be much more biocompatible than Chir nanoparticles while retaining the ability to release the drug with high efficiency, especially towards specific types of cancerous cells.

We previously developed two optimized formulations of dexamethasone acetate (DXMa) hydrogels by means of special cubic mixture designs for topical ocular administration. These gels were elaborated with hydroxypropyl-β-CD (HPβCD) and hydroxypropyl-γ-CD (HPγCD) and commercial hydrogels in order to enhance DXMa water solubility and finally DXMa’s ocular bioavailability and transcorneal penetration. The main objective of this study was to characterize them and to evaluate in vitro, ex vivo, and in vivo their safety, biopermanence, and transcorneal permeation. Gels A and B are Newtonian fluids and display a viscosity of 13.2 mPa.s and 18.6 mPa.s, respectively, which increases their ocular retention, according to the in vivo biopermanence study by PET/CT. These hydrogels could act as corneal absorption promoters as they allow a higher transcorneal permeation of DXMa through porcine excised cornea, compared to DEXAFREE® and MAXIDEX®. Cytotoxicity assays showed no cytotoxic effects on human primary corneal epithelial cells (HCE). Furthermore, Gel B is clearly safe for the eye, but the effect of Gel A on the human eye cannot be predicted. Both gels were also stable 12 months at 25 °C after sterilization by filtration. These results demonstrate that the developed formulations present a high potential for the topical ocular administration of dexamethasone acetate.

The aim of the present research work was synthesis of some 2-furyl[(4-aralkyl)-1-piperazinyl]methanone derivatives and to ascertain their antibacterial potential. The cytotoxicity of these molecules was also checked to find out their utility as possible therapeutic agents. The synthesis was initiated by reacting furyl(-1-piperazinyl)methanone (1) in N,N-dimethylformamide (DMF) and lithium hydride with different aralkyl halides (2a-j) to afford 2-furyl[(4-aralkyl)-1- piperazinyl]methanone derivatives (3a-j). The structural confirmation of all the synthesized compounds was done by IR, EI-MS, 1H-NMR and 13C-NMR spectral techniques and through elemental analysis. The results of in vitro antibacterial activity of all the synthesized compounds were screened against Gram-negative (S. typhi, E. coli, P. aeruginosa) and Gram-positive (B. subtilis, S. aureus) bacteria and were found to be decent inhibitors. Amongst the synthesized molecules, 3e showed lowest minimum inhibitory concentration MIC = 7.52±0.μg/mL against S. Typhi, credibly due to the presence of 2-bromobenzyl group, relative to the reference standard, ciprofloxacin, having MIC = 7.45±0.58μg/mL. [ABSTRACT FROM AUTHOR]

Mononuclear trans-Pd(II)-NHC complexes (where NHC = N-heterocyclic carbene) bearing asymmetrically substituted NHC-ligand have been synthesized via transmetalation reaction between Ag(I)-NHC complexes and [Pd(NCCH3)2Cl2]. The NHC precursors are accessible in two steps by N-n-alkyl reactions of benzimidazole. The resultant benzimidazolium salts were deprotonated with Ag2O by in situ deprotonation to facilitate the formation of mononuclear Ag(I)-NHC complexes. Single-crystal structural study for Pd(II)-NHC shows that the palladium(II) ion exhibits a square-planar geometry of two NHC ligands and two chloride ions. The cytotoxicity study was investigated against breast cancer cell line (MCF-7). The Ag(I)-NHC complexes exhibit better activities than their corresponding Pd(II)-NHC complexes, whereas all benzimidazolium salts are inactive toward MCF-7 cancer cell line. [ABSTRACT FROM AUTHOR]