Synthesis, biological evaluation and molecular docking study of pyrimidine linked thiazolidinedione derivatives as potential antimicrobial and antitubercular agents.

The design and development of novel antimicrobial agents are highly desired to combat the emergence of medication resistance against microorganisms that cause infections. A series of new pyrimidine-linked thiazolidinedione derivatives (5a-j) were synthesized, characterized, and their antimicrobial properties assessed in the current investigation. Here, novel pyrimidine-linked thiazolidinedione compounds were designed using the molecular hybridization approach. Elemental and spectral techniques were used to determine the structures of the synthesized hybrids. The majority of compounds showed encouraging antibacterial properties. Among the active compounds, 5g, 5i, and 5j showed 1.85, 1.15, and 1.38 times the activity of streptomycin against S. aureus, respectively, with MIC values of 6.4, 10.3, and 8.6 µM. With MIC values of 10.8, 21.9, and 15.4 µM, respectively, the compounds 5g, 5i, and 5j showed 2.14, 1.05, and 1.50 times the activity of linezolid against the methicillin-resistant S. aureus (MRSA) strain. Furthermore, when compared to the reference medications, compounds 5g, 5i, and 5j demonstrated broad-range antimicrobial efficacy against all tested strains of bacteria and fungus. Out of all the compounds that were investigated, compounds 5g, 5i, and 5j showed noteworthy anti-tubercular activity. 5g is the most effective, 1.59 times more effective than reference drug isoniazid. To anticipate the binding manner, the synthesized potent compounds were subjected to molecular docking into the active binding site of MRSA and the mycobacterial membrane protein large 3 (MmpL3) protein. The compounds 5g, 5i, and 5j may eventually serve as lead compounds in the search for antimicrobial and anti-TB therapeutic agents.

Synthesis, antitubercular profile and molecular docking studies of quinazolinone-based pyridine derivatives against drug-resistant tuberculosis.

The promising quinazolinone-based pyridine derivatives (4a-j) were synthesized and subsequently tested for their antimycobacterial activities against the various drug-sensitive and drug-resistant Mycobacterium tuberculosis (Mtb) strains to combat infectious diseases and address growing concerns about the devastating effects of tuberculosis (TB). Utilizing 1H NMR, 13C NMR, and mass spectra, the structural and molecular confirmation of the synthesized compounds were deciphered. With minimum inhibitory concentration (MIC) values ranging from 0.31 to 19.13 µM, the results showed that compounds 4e and 4f showed promise anti-TB action against both drug-sensitive and drug-resistant TB strains. To study the cytotoxicity of synthesized molecules, normal Vero and mouse macrophage (RAW264.7) cell lines were utilized. Remarkably, it was revealed that at the highest concentration tested, none of the newly synthesized molecules were toxic to the Vero cell line. The binding patterns of the potent compounds 4b, 4e and 4f in the active site of the mycobacterial membrane protein Large 3 (MmpL3) protein are also revealed by molecular docking studies, which has contributed to the development of a structural rationale for Mtb inhibition. The physicochemical characteristics of the compounds were then predicted using theoretical calculations. Overall, the molecular docking results, physiochemical properties, and observed antimycobacterial activity all point to compound 4e with trifluoromethyl and compound 4f with nitro moiety as potential quinazolinone linked pyridine-based MmpL3 inhibitors.Communicated by Ramaswamy H. Sarma.

Design, synthesis, anticancer activity and docking studies of novel quinazoline-based thiazole derivatives as EGFR kinase inhibitors.

The in vitro anticancer efficacy of a new series of quinazoline-based thiazole derivatives was explored. Three cancer cell lines, MCF-7, HepG2, and A548, as well as the normal Vero cell lines, were tested employing the synthesized quinazoline-based thiazole compounds (4a-j). All of these compounds showed a moderate to significant cytotoxic impact that would have been noticeable and, in some cases, much more pronounced than the widely used drug erlotinib. For the MCF-7, HepG2, and A549 cell lines, respectively, the IC50 values of compound 4i were 2.86, 5.91, and 14.79 µM while those of compound 4j were 3.09, 6.87, and 17.92 µM. For their in vitro inhibitory effects against different EGFR kinases, such as the wild-type, L858R/T790 M, and L858R/T790 M/C797S, all the synthesized compounds were tested. The IC50 values for compound 4f against the wild-type, L858R/T790 M, and L858R/T790 M/C797S mutant EGFR kinases were 2.17, 2.81, and 3.62 nM, respectively. Investigations on the molecular docking of significant molecules indicated potential mechanisms of binding into the EGFR kinase active sites. By using in-silico simulations, compounds' putative drug-like qualities were verified. Finally, it has been shown that the newly synthesized compounds 4i and 4j are good candidates and beneficial for future design, optimization, and research to build more potent and selective EGFR kinase inhibitors with higher anticancer activity.

Ultrasound assisted fabrication of InVO4/In2S3 heterostructure for enhanced sonophotocatalytic degradation of pesticides.

A cost effective and environmentally benign ultrasonic method has been developed for the synthesis of InVO4 (InV), In2S3 (InS) and the InVO4/In2S3 heterostructure (InV/InS). All the designed materials were evaluated for their structural, morphological, spectroscopic, and electrochemical characterizations. Materials were examined for photocatalytic, sonocatalytic, and sonophotocatalytic degradation of carbofuran (CBF) and diazinon (DZN) pesticides under visible light. InV/InS showed enhanced degradation of CBF and DZN when compared to InV and InS. Photocatalytic degradation was accelerated by ultrasonication and found to degrade 97 and 98 % of CBF and DZN in 60 and 70 min, respectively. The reaction conditions, like pH, catalyst dosage, acoustic intensity, and ultrasound power, were carefully optimized. Electron spin resonance (ESR) spectroscopy shows the generation of superoxide radical anion and hydroxyl radicals as reactive species during photoredox reaction. The CBF and DZN degradation intermediates were analyzed using liquid chromatography mass spectroscopy (LC-MS) that shows the mineralization of the CBF and DZN to CO2 and H2O. The effect of Cl-, and PO43- were examined towards degradation of CBF and DZN under optimal conditions in the presence of InV/InS. The degradation of CBF and DZN is decreased in presence of Cl-, CO32- and NO3- but PO43- ions does not show any effect on degradation. The bandgap and Mott-Schottky results suggest the existence of type-II heterostructure between InV and InS through the interface. The synthesis of heterostructure and degradation of pesticides utilizes ultrasonic waves, which prove their multiple applications and attract researchers towards the effective use of sonication.

Theoretical and experimental investigation of novel quinazoline derivatives: synthesis, photophysical, reactive properties, molecular docking and selective HSA biointeraction.

Two new quinazoline derivatives (2a and 2b) were successfully synthesized in this work using the condensation technique in excellent yields. Using spectroscopic techniques and elemental analyses, the compounds were completely characterized. Density functional theory (DFT) computations have been used to examine the title compound's reactive characteristics. Chemical reactivity was predicted using local reactive descriptors and molecule electrostatic potential. Additionally, Time dependent DFT (TD-DFT) simulations were used to examine the impact of solvents on the photophysical characteristics. The affinity of compounds 2a and 2b for human serum albumin (HSA) was further explored using several electronic spectroscopies. Through static mechanisms, both compounds reduce the intrinsic fluorescence of HSA. It is determined that the HSA-2b complex's binding constant is significantly greater than the HSA-2a complex. The fluorescence spectrum measurements proved that the HSA underwent structural changes after interaction with these compounds. It was demonstrated by site marker competitive displacement studies that compounds 2a and 2b preferred to bind to site I in HSA subdomain IIA. Additionally, synchronised fluorescence spectra were utilized to analyze how HSA's conformation changed after interacting with various substances. The molecular docking investigations of these compounds with the three critical HSA binding sites, comprising subdomains IIA, IIIA, and IB, further confirmed the experimental findings. The significant contact between the investigated compounds and HSA was supported by the docking simulations.Communicated by Ramaswamy H. Sarma.

Synthesis, molecular docking study and anticancer activity of novel 1,3,4-oxadiazole derivatives as potential tubulin inhibitors.

The current study reports on the synthesis and anticancer efficacy of novel oxadiazole derivatives (8a-f) as tubulin polymerization inhibitors. NMR, mass, and elemental studies were used to confirm the newly produced compounds. In contrast to the conventional medicine colchicine, compounds 8e and 8f demonstrated stronger sensitivity and improved IC50 values in the range of 3.19-8.21 µM against breast MCF-7, colorectal HCT116, and liver HepG2 cancer cell lines. The target compounds were tested for enzymatic activity against the tubulin enzyme. Compounds 8e and 8f were shown to have the most effective inhibitory action among the new compounds, with IC50 values of 7.95 and 9.81 nM, respectively. As compared to the reference drug, molecular docking investigations of the developed compounds revealed the crucial hydrogen bonding in addition to the hydrophobic interaction at the binding site, assisting in the prediction of the structural requirements for the found anticancer activity. These findings indicate that the 1,3,4-oxadizole scaffold has the potential for future research into new anticancer medicines.

Fabrication of layered In2S3/WS2 heterostructure for enhanced and efficient photocatalytic CO2 reduction and various paraben degradation in water.

Because of the excessive use of fossil fuels, CO2 emissions into the environment are increasing. An efficient method of converting CO2 to useful carbonaceous products in the presence of light is one way to address the issues associated with energy and environmental remediation. In2S3/WS2 heterostructure has been fabricated using the efficient hydrothermal method. The results of structural, morphological, optical, and photo/electrochemical characterization confirm the formation of a hierarchical, layered heterostructure of type-II. Enhanced photocatalytic activity is observed in InS/WS heterostructure compared to pristine In2S3 and WS2. InS/WS heterostructure exhibit higher photocatalytic activity than pure In2S3 and WS2. For 12 h, photocatalytic CO2 reduction produces 213.4 and 188.6 µmol of CO and CH4, respectively. Furthermore, the photocatalytic ability of the synthesized materials to degrade different parabens (Methyl: MPB, Ethyl: EPB, and Benzyl: BPB) under visible radiation was evaluated. Under optimized conditions, the InS/WS heterostructure degraded 88.6, 90.4, and 95.8% of EPB, BPB, and MPB, respectively, in 90 min. The mechanism of photocatalysis was discussed in detail. MCF-7 cell viability was assessed and found to exhibit low mortality in InS/WS treated MPB aqueous solution. InS/WS heterostructure could improve the fabrication of more sulphide-based layered materials to combat environmental pollution.

Design, synthesis, molecular docking and pharmacological evaluation of novel triazine-based triazole derivatives as potential anticonvulsant agents.

Triazine-linked triazole compounds (4a-j) were designed, synthesized, and then examined for their anticonvulsant abilities. Compounds 4e, 4f, 4g, 4i, and 4j displayed significant anticonvulsant activity in both maximum electroshock seizure (MES) and pentylenetetrazole (PTZ) induced seizure during the preliminary screening. The phase II anticonvulsant activity statistics revealed that compounds 4e, 4f, 4g, 4i, and 4j demonstrated excellent activity as compared to the conventional drugs methaqualone and valproate, supporting the potential of these triazine-linked triazole analogues as novel anticonvulsant agents. To take use of the findings, computational parameters including docking analysis and drug-likeness prediction were carried out. Molecular modelling studies supported the essential pharmacophoric information that the structure activity relationship offered. The triazine-linked triazole analogues that were investigated might be viewed as helpful models for future research and derivatization.

Gadolinium sesquisulfide anchored N-doped reduced graphene oxide for sensitive detection and degradation of carbendazim.

Agriculture is having a major role in solving issues associated with food shortages across the globe. Carbendazim (CZM) is one of the fungicides which is commonly used in agriculture to grow crops in large quantities and fast. Monitoring CZM content is in high demand for environmental remediation. The present work deals with the synthesis of gadolinium sesquisulfide anchored Nitrogen-doped reduced graphene oxide (Gd2S3/NRGO) through a simple microwave-assisted method. X-ray diffraction and morphological studies confirm the formation of the nanocomposite. Gd2S3/NRGO showed enhanced activity both in electrochemical detection and light-driven degradation of CZM compared to Gd2S3 and NRGO. Gd2S3/NRGO modified glassy carbon electrode (GCE) exhibit a wide linear range of 0.01-450 µM CZM with 0.009 µM LOD using differential pulse voltammetry (DPV). Gd2S3/NRGO@GCE showed good selectivity, stability, and recovery (98.13-99.10%) in the river water sample. In addition, Gd2S3/NRGO has been explored towards the visible-light-induced degradation of CZM. The reactions conditions were optimized to achieve maximum efficiency. 94% of CZM was degraded within 90 min in presence of Gd2S3/NRGO. Mechanism of electrochemical redox reaction and degradation of CZM in presence of Gd2S3/NRGO has been explored to the maximum extent possible. Degradation intermediates were identified using LC-MS.

Microwave-assisted N-alkylation of amines with alcohols catalyzed by MnCl2 : Anticancer, docking, and DFT studies.

A new protocol for the N-alkylation of amines with alcohols for the synthesis of tertiary amines in the presence of MnCl2 as a catalyst, under microwave conditions, is described. The advantages of this protocol include stable reaction profiles, a wide substrate variety, excellent yields, low cost, high yields, and easy workup conditions. The anticancer efficacy of all the synthesized compounds was tested in vitro against various cancer cell lines, such as MCF-7, MDA-MB-231 (human breast), HT-29, HCT 116 (colon cancer), A549 (human lung carcinoma), and Vero cells. Among the screened compounds, 3e, 3h, and 3i demonstrated potent anticancer activity, with compound 3h surpassing the reference drug cisplatin against A549, MCF7, MDA-MB-231, and HCT116 cancer cells. The introduction of an electron-withdrawing group on the phenyl ring resulted in increased anticancer activity. The most potent compounds, 3e, 3h, and 3i, were tested against VEGFR-2, HER2, and EGFR in multikinase inhibition assays, with compounds 3h and 3i showing improved potency against the HER2 kinase. The compounds formed two H-bonds with amino acids, indicating that they had a high affinity for the target HER2 kinase (PDB ID: 3RCD), according to the docking analysis. The absorption, distribution, metabolism, excretion, and toxicity properties of the optimized analogs were also assessed in vitro, enabling the discovery of promising anticancer agents. Finally, the B3LYP level was used to measure density functional theory geometry optimization and the related quantum parameters for the active compounds.

Design, synthesis and molecular docking studies of imidazole and benzimidazole linked ethionamide derivatives as inhibitors of InhA and antituberculosis agents.

To explore effective antituberculosis agents, a new class of imidazoles and benzimidazoles linked ethionamide analogs were designed and synthesized. The elemental analysis, 1H NMR, 13C NMR and mass spectral data were used to characterize all of the novel analogs. In vitro activity against Mycobacterium tuberculosis (Mtb) H37Rv was assessed for all of the target compounds. The hydroxy and nitrile moieties on the imidazole ring, as well as the hydroxy and methoxy groups on the benzimidazole ring connected to the ethionamide side chain, were shown to be advantageous. In our cell viability experiment against the Vero cell line, all of the compounds were non-cytotoxic even at 100 µM. To confirm the powerful analogs target identification, we investigated their in vitro inhibitory action on an M. tuberculosis InhA over-expressing (Mtb InhA-OE) strain, which yielded MICs nearly twice those of the Mtb H37Rv strain. Furthermore, the results of molecular docking confirmed the experimental findings. Additionally, the molecules were evaluated in silico for ADMET and drug similarity features. The experimental observation enables the newly generated ethionamide derivatives to be attractive candidates for the creation of newer and better anti-TB agents.

Nitrogen doped carbon spheres from Tamarindus indica shell decorated with vanadium pentoxide; photoelectrochemical water splitting, photochemical hydrogen evolution & degradation of Bisphenol A.

At present energy and environmental remediation are of highest priority for the well defined sustainability. Multifunctional materials that solve both the issues are on high demand. In the present work, a simple method has been followed to extract carbon spheres fromTamarindus indica(commonly known astamarind fruit) shelland doped with nitrogen (N-CS). Vanadium pentoxide nanoflakes were decorated aroundN-CS and the resultant is labeled as V2O5/N-CS nanocomposite. The spectroscopic, microscopic, elemental mapping and x-ray photoelectron spectroscopic characterization confirm the nitrogen doping and formation of hybrid material. N-CS, V2O5, and V2O5/N-CS nanocompositehave been evaluated for their efficiency to evolve hydrogen and for degradation of Bisphenol A (BPA) under visible light. In addition, electrocatalytic hydrogen evolution in presence of light has also been evaluated. The DRS spectrum proves the decrease in the bandgap of V2O5 upon its decoration around N-CS material. In a photochemical experiment, the V2O5/N-CS nanocomposite evolved 18,600 µmolg-1 of H2.Electrochemical hydrogen evolution has also been evaluated in presence of light and obtained the onset potential of -60mV with 52 mV dec-1 Tafel slope value. Scavenger studies indicate superoxide radicals and hydroxyl radicals are the active species responsible for the degradation of BPA. BPA degradation pathway has been predicted with the support of LC-MS results of the intermediates. All these results indicate the synthesized nanocomposite could be an efficient, stable multifunctional material for photocatalytic applications.

Discovery of a novel series of substituted quinolines acting as anticancer agents and selective EGFR blocker: Molecular docking study.

A Ta2O5-anchored-piperidine-4-carboxylic acid (PPCA) nanoparticle has been synthesized and characterized. It was then used as a highly effective nanocatalyst for the synthesis of quinolin-2(1H)-one derivatives through CO bond functionalization. The special advantage of this heterogeneous solid catalyst is the reusability of the catalyst for up to five cycles without any noticeable reduction in product yields. In comparison, healthy reaction profiles, wide substrate scope, excellent yields and easy workup conditions are the notable highlights of this approach. All the compounds were tested for their anticancer activity against MCF-7 (human breast), HepG2 (human liver), HCT116 (human colorectal), and PC-3 (human prostate) cancer cell lines with the MTT assay. All the compounds were shown to have moderate to good inhibitory effects on tested cancer cell lines. Besides, compounds 5b, 5c and 5d showed good selectivity against epidermal growth factor receptor-tyrosine kinase (EGFR-TK). Molecular docking results showed that active compounds showed a good affinity towards EGFR kinase (PDB ID: 6V6O) by forming two hydrogen bonds with Cys-797 and Tyr-801. All the compounds were screened for computational ADMET and Lipinski analysis.

Click synthesis of 1,2,3-triazole based imidazoles: Antitubercular evaluation, molecular docking and HSA binding studies.

Using Cu(I)-catalyzed cycloaddition of alkyne and azide reaction (CuAAC), a series of novel 1,2,3-triazole based imidazole derivatives (3a-e) have been synthesized. The synthesized molecules were characterized by spectroscopic techniques such as 1H NMR, 13C NMR, mass and elemental analysis. Antitubercular activity (anti-TB) against Mycobacterium tuberculosis H37Rv (Mtb) and cytotoxic activity against the mammalian Vero cell line was screened for the synthesized compounds. The compounds 3d and 3e displayed potent in vitro antitubercular activity and may serve as a lead for further optimization. Besides, the experimental findings were in line with the results of molecular docking. Also, the synthesized compounds have also been analyzed for ADME properties and the experimental finding facilitates the development of new and more potent anti-TB agents in this series in the future. Using fluorescence and UV-vis absorption spectroscopy, the binding interaction of compounds (3d and 3e) with human serum albumin (HSA) was investigated. The results showed that, as a result of HSA-compound complex, the fluorescence quenching of HSA by test compounds was a static quenching process. According to Forster's theory, energy transfer efficiency is calculated.

Synthesis, Characterization, and BSA Binding Studies of Some New Benzamides Related to Schiff Base.

Condensation of amine 1 with aldehyde 2 gives Schiff base, N-(4-((benzofuran-2-ylmethylene) amino)phenyl)acetamide 3. Schiff base on N-acylation with different substituted acid chlorides in the presence of triethylamine gives the corresponding benzamides, N-acetyl-N-(4-((benzofuran-2-ylmethylene)amino)phenyl)substitutedbenzamide (NABP) 5a-j. The structures of newly synthesized compounds were characterized by elemental analysis, (1)H NMR, (13)C NMR FT-IR, and mass spectral studies. Compounds 3 and 5a-j have been screened for their antimicrobial activity using the disc diffusion and minimum inhibitory concentration (MIC) method against the selected bacterial and fungal strain. Compounds 5a, 5e, 5g, and 5h were found to be more active against all tested strains. The antioxidant properties were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging methods. Compounds 5i and 5j showed predominant antioxidant activities among the synthesized analogues. The interaction between NABP and bovine serum albumin (BSA) was investigated using fluorescence and ultraviolet spectroscopic techniques at 298 K under imitated physiological conditions. The results revealed that NABP caused the fluorescence quenching of BSA through a static quenching procedure. The binding constants and the number of binding sites were calculated. The binding distance between the donor (BSA) and acceptor (NABP) was determined based on Forster's theory.

Synthesis, anticonvulsant, antioxidant and binding interaction of novel N-substituted methylquinazoline-2,4(1H,3H)-dione derivatives to bovine serum albumin: a structure-activity relationship study.

A novel class of N-substituted glycosmicine derivatives was synthesized, and their anticonvulsant, antioxidant activity and interaction with bovine serum albumin (BSA) were evaluated. The synthesized compounds 4a-j were examined for anticonvulsant activity by maximal electroshock induced seizures (MESs) test and their neurotoxic effects were determined by rotorod test in mice. The structure-activity relationships (SARs) of these compounds were also investigated. Compounds 4d, 4g, 4i and 4j were found to have good protective effect from seizure. The in vitro antioxidant activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radical scavenging assay. The interaction between novel N-substituted methylquinazoline-2,4(1H,3H)-dione (NMQ) and BSA was analyzed by fluorescence and ultraviolet spectroscopy at 304K under simulative physiological conditions. BSA fluorescence quenched by NMQ is discussed according to the Stern-Volmer equation. The binding constant and binding sites of NMQ with BSA were calculated. According to Forster non-radiation energy transfer theory, the binding distance (r) between NMQ and BSA was calculated.

Synthesis, characterization, antidepressant and antioxidant activity of novel piperamides bearing piperidine and piperazine analogues.

A series of piperamide derivatives (8a-j) was synthesized with various substituted piperidine and piperazine compounds. The prepared compounds were evaluated for antibacterial activity against gram-positive and gram-negative bacteria and antifungal activity by disc diffusion method. The antioxidant activity of the compounds was evaluated by DPPH and superoxide radical scavenging method and antidepressant activity using forced swim and tail suspension behavioral despair tests in mice. The compounds 8a, 8b and 8c were investigated for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory property. Some of the test compounds were active in forced swim test (FST) and tail suspension test (TST). Compounds 8a and 8b showed a significant effect, when compared to standard drug, clorgyline.