Good Binding Energy Research Articles

Exploring Highly Functionalized Tetrahydropyridine as a Dual Inhibitor of Monoamine Oxidase A and B: Synthesis, Structural Analysis, Single Crystal XRD, Supramolecular Assembly Exploration by Hirshfeld Surface Analysis, and Computational Studies.

Ethyl 4-(4-fluorophenylamino)-2,6-bis(4-(trifluoromethyl)phenyl)-1-(4-fluoro-phenyl)-1,2,5,6-tetrahydropyridine-3-carboxylate (FTEAA) has been synthesized efficiently in an iodine-catalyzed five-component reaction of 4-fluoroaniline, 4-trifluoromethyl benzaldehyde, and ethyl acetoacetate in methanol at 55 °C for 12 h. Various spectro-analytical techniques such as 1H and 13C NMR and Fourier-transform infrared spectroscopy have validated the structure of FTEAA. Further confirmation of the structure of FTEAA has been established on the basis of single-crystal X-ray diffraction analysis. The supramolecular assembly of FTEAA in terms of strong and comparatively weak noncovalent interactions is fully investigated by Hirshfeld surface analysis, the interaction energy between pairs of molecules, and energy frameworks. The void analysis is conducted to explore the strength and stability of the crystal structure. Furthermore, molecular docking analysis was computationally performed to see the potential intermolecular interactions between the selected proteins and FTEAA. The binding interaction energies are found to be −8.8 and −9.6 kcal/mol for the proteins MAO-B (PDB ID: 2V5Z) and MAO-A (PDB ID: 2Z5X), respectively. These reasonably good binding energies (more negative values) indicate the efficient associations between the FTEAA and target proteins. The proteins and FTEAA were also analyzed for intermolecular interactions. FTEAA and proteins interact in a variety of ways, like conventional hydrogen bonds, carbon–hydrogen bonds, alkyl, π-alkyl, and halide interactions.

Design and synthesis of novel quinazolinyl-bisspirooxindoles as potent anti-tubercular agents: an ultrasound-promoted methodology.

The essential need for the potent anti-tubercular (anti-TB) agents with high selectivity and safety profile prompted us to synthesize a new series of quinazolinyl-bisspirooxindoles. The title compounds were synthesized by one-pot multicomponent [3 + 2] cycloaddition reaction under ultrasonication. Further, in vitro anti-TB activity was evaluated against Mycobacterium tuberculosis H37Rv. Among the screened compounds, two compounds (4q and 4x) showed potent activity with MIC value 1.56µg/mL and four compounds exhibited significant activity (MIC = 3.125µg/mL), and also cytotoxicity studies against RAW 264.7 cell lines reveal that most active compounds were less toxic to humans. In addition, in order to demonstrate the inhibitory properties, molecular docking studies were carried out and the results showed that the target compounds have good binding energy and better binding affinity within the active pocket, thus these compounds may consider to be as potent inhibitors toward selective targets.

Evaluation for substitution of stem bark with small branches of Cassia fistula Linn for traditional medicinal uses: A comparative chemical profiling studies by HPLC, LC-MS, GC-MS

BackgroundThe Aim of the present research article is to proposing a conservative approach for the Cassia fistula by using of small branches instead of stem bark because of plant has many important chemical constituents which show different medicinal activity so consumption of plant is high. We studied here Comparative preliminary phytochemical screening test of the ethanol extract and aqueous extract of the stem bark and small branches of Cassia fistula obtained by cold maceration process. Physicochemical analysis of Cassia fistula was done to ascertain the quality of the raw material used in the study. Successive soxhlet extraction method used for the successive extraction of stem bark and small branches with different solvents for comparative chemical profile study by HPLC, LCMS, and GCMS. Molecular Docking Interaction of Abundant Medicinal Phytochemicals in the Liquid Chromatography−Mass Spectrometry (LC−MS) Analysis Data of C. fistula with the L. donovani Drug Target Proteins and Pancreatic lipase colipase target protein. ResultThe pH of the small branches was found slightly higher as compared to stem bark and the percentage of other parameters like total ash content, acid insoluble ash, loss on drying at 105 °C, water soluble extractive and alcohol soluble extractive values were found fewer in the small branches as compare to stem bark of the plant. It was observed that the number of peaks in stem bark and small branches of the plant sample were almost similar and the retention time of each peak in stem bark was coincide with the retention of small branches of the sample. Therefore, similarity was observed in stem bark and small branches of the Cassia fistula plant in HPLC, LC-MS and GC-MS. The results obtained from HPLC analysis shows that stem bark contains 0.0084% and small branches having 0.0257% of rhein in Cassia fistula. Compounds 3, 9 and 12 are present in Stem bark as well as small branches of C. fistula and Compounds 22, 32 and 37 are present in small branches only. All the compounds have very good binding energy (Kcal/mol) with the respective target proteins. ConclusionThe small branches have more active chemical constituents than stem bark against particular target proteins.

Synthesis, spectral characterization, crystal structure and computational investigation of 2-formyl-6-methoxy-3-carbethoxy quinoline as potential SARS-CoV inhibitor

The recent COVID-19 outbreak caused by the novel coronavirus SARS-CoV-2 has an immense impact on global health and economy. Although vaccines are being used, urgent need of drugs based on natural products with high efficacy and safety is a pressing priority. Quinoline alkaloids are well known for their therapeutic action against malaria; initially, it was tried against Coronaviruses. It is a basic vital scaffold to design drugs with required biological and pharmacological activities. In this present study, a new quinoline compound was synthesized and characterized by spectroscopy techniques. Crystal structure was established by SCXRD analysis and data is used as an input to perform various computations. Additionally, using state-of-the-art quantum computational techniques, the geometry optimization and calculation of UV–Vis spectrum of 2F6M3CQ were performed at B3LYP/6-311G* level of theory. The optimized molecular geometric parameters as well as UV–Vis spectrum values are found to be in good agreement with their respective experimental results. The visualization of 3-D plots of FMO and MEP indicated the structure and reactivity trends of 2F6M3CQ molecule. Molecular docking methods were utilized to find the drug ability of 2F6M3CQ with Mproprotein of SARS-CoV-2. There were many intermolecular interactions between Mpro protein and 2F6M3CQ molecule which lead to good binding energy (−5.5 kcal/mol) between them which was found to be better than the binding energy of chloroquinine molecule (−4.5 kcal/mol) as studied under same docking protocols. Finally, drug likeness and ADME properties of 2F6M3CQ were also analyzed. There is no violation found for RO5 in our 2F6M3CQ compound. ADME analysis shows drug like properties of compound 2F6M3CQ which predicts that it might be a potential candidate for inhibition of SARS-CoV-2.

New 1,2,3-Triazole-genipin Analogues and Their Anti-Alzheimer's Activity.

A novel series of 1,2,3-triazole-genipin analogues were designed, synthesized, and evaluated for neuroprotective activity, acetylcholinesterase (AChE), and butyrylcholinesterase (BuChE) inhibitory activity. The genipin analogues bearing bromoethyl- and diphenylhydroxy-triazole showed in vitro neuroprotective properties against H2O2 toxicity along with potent inhibitory activity on BuChE with IC50 values of 31.77 and 54.33 μM, respectively, compared with galantamine (IC50 = 34.05 μM). The molecular docking studies of these genipin analogues showed good binding energy and interact well with the key amino acids of BuChE via hydrogen-bonding and hydrophobic interactions. Triazole genipins might be promising lead compounds as anti-Alzheimer’s agents.

Synthesis, anticancer activity and docking studies of pyrazoline and pyrimidine derivatives as potential epidermal growth factor receptor (EGFR) inhibitors

A search for anticancer agents has prompted the design and synthesis of new chalcone, pyrazoline and pyrimidine derivatives as potential epidermal growth factor receptor (EGFR) kinase inhibitors. These derivatives’ binding affinities were predicted by AutoDock, which showed that chalcone, pyrazoline and pyrimidine derivatives as EGFR-kinase inhibitors have good binding energies, ranging from −10.91 to −7.32 kcal/mol. These compounds were synthesized and characterized using elemental analysis (CHN analysis) and spectroscopic techniques (FTIR and NMR). Among the pyrazoline derivatives, 4Aiii has revealed a superior in vitro activity, inhibiting the EGFR kinase even at a low concentration of 0.19 μM compared to the pyrimidine derivative, 5Bii. In contrast, the cytotoxic effect of these derivatives was studied against hormonal and non-hormonal breast cancer cell lines. Most of the pyrazoline derivatives were able to express their cytotoxic effect efficiently against hormonal breast cancer but only one pyrimidine derivative managed to express its activity against hormonal breast cancer.

Chemical Composition, In Silico and In Vitro Antimutagenic Activities of Ethanolic and Aqueous Extracts of Tigernut (Cyperus esculentus).

Tigernut, also known as Cyperus esculentus, is said to be high in nutritional and medicinal value. The purpose of this study was to determine the C. esculentus’s antimutagenic activity. The ethanolic and aqueous extracts of the nut were analyzed for chemical constituents, antioxidants, ultraviolet-visible, and gas chromatography-mass spectrometry using standard procedures. The extracts contained a total of 17 major compounds that were docked against human RecQ-like protein 5 (RECQL5) helicase protein. The antimutagenic property of the ethanolic extract in vitro was assessed using the Allium cepa chromosome assay. Onion bulbs were pre-treated with 200 mg/kg of ethanolic extract of C. esculentus for 24 h and then, grown in NaN3 (250 μg/L) for 24 h; onion bulbs were also first exposed to NaN3 (250 μg/L) for 24 h before treatment with 100 mg/kg and 200 mg/kg of the ethanolic extract respectively. Standard methods were used to determine the mitotic index and chromosomal aberrations. Results revealed that C. esculentus ethanolic extract contained flavonoids (22.47 mg/g), tannins (0.08 mg/g), alkaloids (19.71 mg/g), glycosides, phenol, and tannin and showed high scavenging activity against 2,2-diphenyl-1-picrylhydrazyland H2O2. Docking with RECQL5 showed good binding energies (∆G>−7) of five compounds in C. esculentus ethanolic extract. The A. cepa assay results revealed a significant (P<0.05) reduction in chromosomal aberrations and a higher mitotic index in groups treated with the C. esculentus ethanolic extract. The antimutagenic activity of C. esculentus ethanolic extract was attributed to its high levels of phytosterols and phenolic compounds.

Synthesis, in vitro evaluation and molecular docking studies of novel naphthoisoxazolequinone carboxamide hybrids as potential antitumor agents

Based on previous results with benzoindazolequinone (BIZQ) derivatives, a new series of bioisosteric 3-methylnaphtho[2,3-d]isoxazole-4,9-quinones (NIQs), conjugated with C-protected amino acids as glycine (Gly), L-alanine (Ala), L-phenylalanine (Phe) and L-glutamic acid, were synthesized from NIQ 2, and the chemical structures of intermediates and hybrids were elucidated by spectroscopic techniques. The antiproliferative activity of NIQs was evaluated by in vitro assay on cultured MCF-7 breast adenocarcinoma and KATO III gastric carcinoma cells. All the compounds showed to be cytotoxic against both cell lines, with IC50 values between 22.9 and 215.3 µM. NIQ hybrids 6, 8, and 9, conjugated with Gly, Phe and Glu, respectively, showed to be more cytotoxic, and hybrid 8 also proved to have higher activity than the precursor 2 against MCF-7 cells. Docking studies showed that NIQs exhibited very good binding energies (ΔG bin ) in the active site of proteins that participate in key carcinogenic pathways.

GC-MS/MS Quantification of EGFR Inhibitors, β-Sitosterol, Betulinic Acid, (+) Eriodictyol, (+) Epipinoresinol, and Secoisolariciresinol, in Crude Extract and Ethyl Acetate Fraction of Thonningia sanguinea.

Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS/MS) was used to quantify epipinoresinol, β-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of −19.93 and −16.63 Kcal/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments.

In silico Approach and Molecular Docking Studies of Potent Bioactive Compounds of Carica papaya as Anti-breast Cancer Agents.

Breast cancer is one of the greatest global dilemmas, and the current treatment option is to target hormone receptors with partial agonists/antagonists. Estrogen and aromatase enzymes play important roles in breast cancer. Excessive estrogen activity or inadequate estrogen production leads to various hormonal issues, including breast cancer. Potent breast cancer drugs are Tamoxifen, Paclitaxel, Cyclophosphamide, Trastuzumab, etc., and aromatase inhibitors, include Anastrozole, Letrozole, and Exemestane, etc. In general, breast cancer drugs cause numerous adverse effects in humans. This study has attempted to identify alternative drug candidates from Carica papaya for treating breast cancer with fewer side effects. To achieve this, we have utilized computational methods to predict the characteristics of bioactive compounds from Carica papaya and determine the target binding affinities using the Schrödinger suite (Maestro 9.5). The target protein and ligands were obtained from the well-known database. Carica papaya has 35 identified bioactive compounds that were drawn using ChemDraw software and performed Ligand preparation wizard. Absorption, Distribution, Metabolism, and Excretion (ADME) analysis is performed with QikProp. From the docking studies, the phytocompounds such as Chlorogenic acid, Myricetin, Quercetin, Isorhamnetin, and Catechin showed the highest Glide scores (G Score). Among the five bioactive phytocompounds, Chlorogenic acid has a higher G Score with good binding energy than Tamoxifen, Anastrozole, and Letrozole standards. The pharmacokinetic properties and drug-likeness of phytocompounds were determined using ADME profiling. Carica papaya phytocompounds serve as an antiestrogen or aromatase inhibitor that regulates estrogen levels to reduce the risk of breast cancer in postmenopausal women. As a result, we recommend that these top five bioactive phytocompounds be investigated further in in vitro and in vivo studies.

Uncovering the mechanism of Huanglian-Wuzhuyu herb pair in treating nonalcoholic steatohepatitis based on network pharmacology and experimental validation

Ethnopharmacological relevanceThe Huanglian-Wuzhuyu herb pair (HWHP) is a classic Chinese herbal formula consisting of the root of Coptis chinensis Franch and dried, nearly mature scented fruit of Tetradium ruticarpum (A.Juss.) T.G.Hartley. It is widely utilized to treat gastrointestinal and liver diseases such as diarrhea, dysentery, cholestasis, hepatocellular carcinoma, and nonalcoholic steatohepatitis (NASH). However, the mechanism of HWHP in treating NASH remains poorly understood. Aim of the studyThis study investigated the mechanisms of HWHP in NASH treatment via network pharmacology and validated the results through in vivo experiment using mouse models. Materials and methodsThe compounds and targets corresponding to the active ingredients of HWHP were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The genes associated with NASH were obtained from the DisGeNET database. Cytoscape software was employed to construct a “drug-ingredient-target-disease” network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the related signaling pathways affected by HWHP. Moreover, AutoDock software was used to assess the potential binding affinity between the key targets of the hub pathway and the bioactive compounds. Subsequently, in vivo experiment was conducted to verify the findings of network pharmacology. ResultsA total of 41 active compounds and 198 targets of HWHP were screened, of which 51 common targets were related to NASH. GO functional enrichment analysis revealed that HWHP may affect NASH by modulating inflammatory response. KEGG pathway enrichment suggested that the NOD-like receptor (NLR) signaling pathway may play an important role in treating NASH. Molecular docking results demonstrated that most HWHP components were successfully docked to NLRP3 with good binding energy. In vivo experiments revealed that HWHP alleviated liver inflammation, improved liver steatosis, reduced TC, TG, LDL-C, ALT, and AST, decreased mRNA expressions of IL-6, IL-18, and TNF-α in the liver, and lowered the expressions of NLRP3, pro-IL-1β, and ASC protein. Also, immunohistochemical findings presented downregulation of caspase-1 and IL-1β by HWHP. ConclusionsThe results disclosed that HWHP ameliorates NASH in mice by reducing inflammation and liver steatosis via inhibition of NLRP3 inflammasome. This study revealed the mechanism of HWHP in treating NASH through experiments.

A Combination of Pharmacophore-Based Virtual Screening, Structure-Based Lead Optimization, and DFT Study for the Identification of S. epidermidis TcaR Inhibitors.

The transcriptional regulator (TcaR) enzyme plays an important role in biofilm formation. Prevention of TcaR-DNA complex formation leads to inhibit the biofilm formation is likely to reveal therapeutic ways for the treatment of bacterial infections. To identify the novel ligands for TcaR and to provide a new idea for drug design, two efficient drug design methods, such as pharmacophore modeling and structure-based drug design, were used for virtual screening of database and lead optimization, respectively. Gemifloxacin (FDA-approved drug) was considered to generate the pharmacophore model for virtual screening of the ZINC database, and five hits, namely ZINC77906236, ZINC09550296, ZINC77906466, ZINC09751390, and ZINC01269201, were identified as novel inhibitors of TcaR with better binding energies. Using structure-based drug design, a set of 7a–7p inhibitors of S. epidermidis were considered, and Mol34 was identified with good binding energy and high fitness score with improved pharmacological properties. The active site residues ARG110, ASN20, HIS42, ASN45, ALA38, VAL63, VAL68, ALA24, VAL43, ILE57, and ARG71 are playing a promising role in inhibition process. In addition, we performed DFT simulations of final hits to understand the electronic properties and their significant role in driving the inhibitor to adopt apposite bioactive conformations in the active site. Conclusively, the newly identified and designed hits from both the methods are promising inhibitors of TcaR, which can hinder biofilm formation.

Identification and validation of potent inhibitor of Escherichia coli DHFR from MMV pathogen box

The present study is conducted to find the solution of rising antimicrobial resistance (AMR) in Escherichia coli which is a pathogen responsible for fatal systemic infections in human and animals. The enzyme dihydrofolate reductase (DHFR) is found in all organisms. In this study DHFR of E. coli (ec-DHFR) and human DHFR (h-DHFR) is targeted by novel chemical entities (NCE) from the Pathogen box of Medicines for Malaria Venture, Switzerland (MMV) using molecular modelling. The in-silico studies were further validated by in-vitro assays. The virtual screening of 400 MMV compounds was conducted using PyRx standard tool followed by manual docking of selected compounds by Autodock vina and Ligplot program. The in-silico studies showed good binding energy and strong hydrogen bond in docking of MMV675968 with ec-DHFR and no hydrogen bond with h-DHFR. This was further validated by the Molecular dynamic studies that revealed high binding free energy in ec-DHFR and in-vitro assays that produced good synergy in combination study of MMV675968 with last line (meropenem) and last resort (colistin) antibiotics. The extensive MD simulation and energetic analysis thus concludes that MMV675968 targets ec-DHFR. The combination studies were conducted with MMV675968 and FDA approved drugs against a panel of multidrug resistant Escherichia coli isolates. The synergistic results obtained in combination studies concluded that in-vitro data is consistent with in-silico data and that MMV675968 is a potential lead for future process of antimicrobial drug development against the multidrug resistance E. coli. Communicated by Ramaswamy H. Sarma

One-Pot Synthesis of Novel Hydrazono-1,3-Thıazolıdın-4-One Derivatives as Anti-HIV and Anti-Tubercular Agents: Synthesıs, Bıologıcal Evaluatıon, Molecular Modelling and Admet Studıes

The necessity for newer anti-HIV and anti-tubercular medications has arisen as a result of the prevalence of opportunistic infections caused by HIV (human immunodeficiency virus). A series of ten new hydrazono 1,3-thiazolidin-4-one derivatives were synthesized in one-pot and evaluated for anti-HIV and anti-tubercular activities. Molecular Docking was accomplished with HIV-1 reverse transcriptase protein (PDB ID: 1REV) and Mycobacterium Tuberculosis (M. tuberculosis) H37Rv protein (PDB ID: 2YES) receptors along with drug-likeness and ADMET properties. One-pot synthesis of hydrazono 1,3-thiazolidin-4-one derivatives was carried out by ketones, thiosemicarbazide and ethylchloroacetate with the catalyst of anhydrous sodium acetate. All the synthesized compounds were characterized and evaluated for their in-vitro anti-HIV and also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv. In-silico predicted physicochemical parameters were done by MedChem DesignerTM software version 5.5 and ADMET parameters by pkCSM online tool. Furthermore, molecular docking was performed with pyrx 0.8 by autodock vina software. All the synthesized compounds were characterized and evaluated for their in-vitro anti- HIV activity for inhibition of syncytia formation, which shows KTE1 with EC50 47.95 μM and Selectivity Index (SI) of >4.17 and for inhibition of p24 antigen production EC50 was found to be 80.02 μM and SI of >2.49. The compounds were also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv, in which KTE1 MIC values of 12.5μg/ml with SI of >4.0 and cytotoxicity against Vero cell lines. In-silico predicted physicochemical parameters for synthesized compounds which were found to be drug-like. Furthermore, docking has shown a good dock score and binding energy with anti-HIV and anti-tubercular receptors. From the novel synthesized molecules, none of the molecule is as effective as standards for anti-HIV and anti-tubercular drugs and hence can be further explored for its potential activities. Furthermore, derivatization was made to achieve more potent compounds for anti-HIV and anti-tubercular drugs.

Novel α-Amylase Inhibitor Hemi-Pyocyanin Produced by Microbial Conversion of Chitinous Discards.

α-Amylase inhibitors (aAIs) have been applied for the efficient management of type 2 diabetes. The aim of this study was to search for potential aAIs produced by microbial fermentation. Among various bacterial strains, Pseudomonas aeruginosa TUN03 was found to be a potential aAI-producing strain, and shrimp heads powder (SHP) was screened as the most suitable C/N source for fermentation. P. aeruginosa TUN03 exhibited the highest aAIs productivity (3100 U/mL) in the medium containing 1.5% SHP with an initial pH of 7–7.5, and fermentation was performed at 27.5 °C for two days. Further, aAI compounds were investigated for scaled-up production in a 14 L-bioreactor system. The results revealed a high yield (4200 U/mL) in a much shorter fermentation time (12 h) compared to fermentation in flasks. Bioactivity-guided purification resulted in the isolation of one major target compound, identified as hemi-pyocyanin (HPC) via gas chromatography-mass spectrometry and nuclear magnetic resonance. Its purity was analyzed by high-performance liquid chromatography. HPC demonstrated potent α-amylase inhibitory activity comparable to that of acarbose, a commercial antidiabetic drug. Notably, HPC was determined as a new aAI. The docking study indicated that HPC inhibits α-amylase by binding to amino acid Arg421 at the biding site on enzyme α-amylase with good binding energy (−9.3 kcal/mol) and creating two linkages of H-acceptors.

Synthesis, Molecular Docking Study, and ADMET Properties of New Antimicrobial Quinazolinone and Fused Quinazoline Derivatives

New quinazolinone and fused quinazoline derivatives are prepared from the reaction of 3,1-benzoxazine-3(4H)-one with different amines. Treatment of 3,1-benzoxazinone 3 with hydrazine hydrate afforded 3-amino-quinazolinone derivative 5 which then used as a key synthesis for different Schiff base compounds 6-8. Synthesis of new fused quinazoline derivatives 9, 10 are achieved from the reaction of 3,1-benzoxazinone with cyanoacetohydrazide or thiocarbohydrazide. The chemical structures of the new synthesized compounds were elucidated based on their spectroscopic analysis. Antimicrobial activities of the designated compounds were studied in vitro toward different pathogenic microbes. Drug-likeness and ADMET properties of the new synthesized compounds were calculated to predict the pre-study of clinical phases as drug molecule, and most of the new compounds fit Lipinski rule and have good bioavailability. Molecular docking studies of all new synthesized compounds were performed into the active site of different macromolecules including bacterial and fungus species and exhibiting good binding energy extended from −5.20 to −10.35 Kcal/mol.

Antiproliferative, apoptosis-inducing activity and molecular docking studies of sydnones compounds.

To evaluate the antiproliferative and apoptosis inducing activity of different sydnones on cancer cell lines and their interaction with cancer proteins by molecular docking studies. Antiproliferative activity was carried out by MTT assay and apoptosis inducing activity was performed by DAPI and Annexin V and propidium iodide staining. Molecular docking studies were performed using AutoDock Tools 1.5.6. Pharmacokinetics properties like ADME and toxicity were analysed by pkCSM web server. In this study, four new sydnone compounds 3-(4-nonylbiphenyl-4'-yl) sydnone (MC-182), 3-(4-propylbiphenyl-4'-yl) sydnone (MC-454), 3-(4-hexylbiphenyl-4'-yl) sydnone (MC-433), and 3-(4-methylbiphenyl-4'-yl) sydnone (MC-431) were screened for antiproliferative and apoptotic effect against BT-474 (human breast cancer), HeLa (human cervical cancer) and Jurkat (human myeloid leukemia) Mostly, all the sydnone compounds exhibited decent antiproliferative effectiveness, but compound MC-431, MC-433, and MC-454 showed more antiproliferative activity (IC50 1.71, 10.09 and 2.87 μM against BT-474, Hela and Jurkat cell line, respectively). The changes of morphological characteristics of cancer cells determined by staining techniques indicate the apoptotic cell death. The molecular docking and interaction studies were carried out between sydnones with cancer proteins (epidermal growth factor domain receptor tyrosine kinase [EGF-TK], tumor necrosis factor-alpha [TNF-α] and Caspase3. Among all four sydnone molecules, two compounds MC-454 and MC-431 showed good binding energy with targeted proteins. Drug-like property was predicted by ADME toxicity study. The results indicate sydnone compounds were found to exhibit anticancer activity by inducing apoptosis. The molecular docking study of sydnones with cancer proteins showed a decent interaction affinity. The results of absorption, distribution, metabolism, excretion and toxicity studies by the Insilco approach also proved that MC-454 sydnone showed better In-Vivo administration. Thus, the current research work indicates that these sydnone compounds would be prospective in developing anticancer medicines.

Synthesis, carbonic anhydrase inhibition, anticancer activity, and molecular docking studies of 1,3,4-oxadiazole derivatives.

In this work, we have synthesized various organic compounds possessing 1,3,4-oxadiazole as a core structure and the structure of the newly synthesized target compounds has been revealed using different analytical approaches such as FT-IR, LCMS, and NMR (proton and carbon), respectively. The in vitro carbonic anhydrase potentials of these synthesized 17 different analogues were investigated. The result suggests that compound 7g, a 3-pyridine substituted analogue with an IC50 of 0.1µM, was found to have the most potent carbonic inhibitory activity (11-fold more active) than the positive control (acetazolamide) with an IC50 of 1.1 ± 0.1µM. Besides, among the series 7(a-q) approved in the identification of four potent carbonic anhydrase inhibitors with the IC50 standards varies from 0.1 to 1.0 ± 0.1µM. Additionally, the non-competitive behaviour for potent compound 7g was analysed using the Lineweaver-Burk plot from the kinetic study. Furthermore, the anticancer activity of all the synthesized compounds screened against B16F10 melanoma cells using the MTT assay method. Additionally, the molecular docking studies revealed that 7g inhibitor shows good binding energy as well as good binding interaction pattern along with enzyme.

In silico Inhibition studies of constituents of Abutilon indicum on Xanthine oxidase

Objective: To find out the xanthine oxidase inhibitory potential of constituents reported from the Abutilon indicum through in silico studies as there is traditional claim supporting the use of this plant in treating gout. Method: The 33 constituents of Abutilon indicum were chosen for the study and their drug likeness were read using online application SwissADME. Molecular docking studies were done in Autodock version 1.5.6. The docked samples were viewed using Molegro Molecular Viewer 2.5.0. and Pymol. Allopurinol was used as standard to compare the docking scores of the plant constituents. Results: All the 33 compounds (A1-A33) exhibited drug likeness. Good binding energies were observed for 19 constituents against 3AX7 protein. 6 compounds such as luteolin, beta-amyrin,1-lycoperodine, chrysoeriol, quercetin and flavone possessed binding energies greater than 8 and good inhibition constant values. Conclusion: The constituents of Abutilon indicum has good xanthine oxidase inhibiting potential and can further be developed into a drug candidate against gout.

Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α-glycosidase.

Here, we report the synthesis, characterization, and biological activities of a series of benzimidazolium salts bearing the trifluoromethylbenzyl group. All benzimidazolium salts were characterized by using nuclear magnetic resonance (NMR) (1 H NMR and13 C NMR), Fourier transform-infrared spectroscopy, and elemental analysis techniques. The crystal structures of some of these compounds were obtained by the single-crystal X-ray diffraction method. Furthermore, the acetylcholinesterase (AChE) and α-glycosidase (α-Gly) enzyme inhibition activities of these compounds were investigated. The obtained results revealed that 2e, with Ki value of 1.36 ± 0.34 µM against AChE and 3d with Ki value of 91.37 ± 10.38 µM against α-Gly, were the most potent compounds against both assigned enzymes. It should be noted that most of the synthesized compounds were more potent than standard inhibitor tacrine (TAC) against AChE. In silico studies, we focused on compound 2e, 3d, 3e, and 3f as potent inhibitors of AChE and α-Gly, the compound 2e showed good binding energy (-10.23 kcal/mol), amongthe three selected compounds and positive control (-10.18, -10.08, and -7.37 kcal/mol for 3d, 3f, and TAC, respectively). Likewise, as a result of the same compounds against the α-Gly enzyme, the compound 3d had the highest binding affinity (-8.39 kcal/mol) between the four selected compounds and the positive control (-8.27, -8.10, -8.06, and -7.53 kcal/mol for 3f, 3e, 2e, and acarbose, respectively). From the absorption, distribution, metabolism, excretion, and toxicity analyses, it can be concluded that the compounds under consideration exhibited more drug-likeness properties in the prediction studies compared to positive controls.