Synthesis, antimicrobial activity, molecular docking, molecular dynamics simulation, and ADMET properties of the mannopyranoside derivatives as antimicrobial agents

Journal of Taibah University for Science, Journal Year: 2024, Volume and Issue: 18(1)

Published: March 13, 2024

Multiple diseases are treated with carbohydrate-based medicinal products worldwide. Direct regioselective acylation of methyl α-D-mannopyranoside (MDMP) derivatives 2-6 afforded from the 6-O-butyryl derivative. This isolated 6-O-derivative was converted to 2,3,4-tri-O-acyl derivatives, and resulting compounds were analyzed using FTIR, 1H-NMR, 13C-NMR, elemental analysis. The acylated showed moderate good antimicrobial activity. Cytotoxicity assessment indicated that compound 2 had lowest toxicity. A SAR study demonstrated lauroyl myristoyl acyl chains combined mannopyranose particularly effective against bacteria. In this context, molecular docking analysis crucial interactions involved in assessing binding affinity ligands 1-6 for active sites Escherichia coli (4XO8) Aspergillus flavus (1R51). 100-ns dynamics simulation all stable at site protein 1R51. silico ADMET prediction revealed greater drug similarity MDMP derivatives. results investigation may help create derivative-based multidrug-resistant agents.

Language: Английский

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Integrative Approach for Designing Novel Triazole Derivatives as α-Glucosidase Inhibitors: QSAR, Molecular Docking, ADMET, and Molecular Dynamics Investigations

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(2), P. 261 - 261

Published: Feb. 19, 2024

In response to the increasing prevalence of diabetes mellitus and limitations associated with current treatments, there is a growing need develop novel medications for this disease. This study focused on creating new compounds that exhibit strong inhibition alpha-glucosidase, which pivotal enzyme in control. A set 33 triazole derivatives underwent an extensive QSAR analysis, aiming identify key factors influencing their inhibitory activity against α-glucosidase. Using multiple linear regression (MLR) model, seven promising were designed as potential drugs. Molecular docking dynamics simulations employed shed light mode interaction between ligands target, stability obtained complexes. Furthermore, pharmacokinetic properties assessed predict behavior human body. The binding free energy was also calculated using MMGBSA method revealed favorable thermodynamic properties. results highlighted three high biological activity, affinity target enzyme, suitability oral administration. These offer interesting prospects development effective well-tolerated mellitus.

Language: Английский

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Computational integration for antifungal 1,2,4-triazole inhibitors design: QSAR, molecular docking, molecular dynamics simulations, ADME/Tox, and retrosynthesis studies

Chemical Physics Impact, Journal Year: 2024, Volume and Issue: 8, P. 100502 - 100502

Published: Feb. 16, 2024

Fungal infections are a growing public health problem worldwide. Despite the availability of several medicines, their efficacy is still constrained by fungal resistance. This research conducted 2D/3D-QSAR analysis on twenty-nine triazole molecules previously evaluated for antifungal activity. The HQSAR/B-H, CoMFA and CoMSIA models were built using twenty-three in training set. They show high Q2 values (0.646, 0.564 0.561, respectively) important R2 (0.764, 0.805 0.787, respectively). predictive capacity established was validated external validation; they performed well. contour maps derived from provide more detail to identify favorable unfavorable groupings impacting Then, 4 proposed new with significant activity suggested. In addition, molecular docking results showed good binding energies interactions inhibitors active site receptor studied. dynamics MM/PBSA methods confirmed results. oral bioavailability toxicity ADME/Tox properties. Finally, retrosynthesis method created synthetic pathway candidate inhibitor Z1.

Language: Английский

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Computer-guided identification of novel inhibitors of apoptosis-signaling kinase 1 from Spondia mombim bioactive compounds against colorectal cancer

Egyptian Journal of Medical Human Genetics, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 14, 2025

Abstract Background Apoptosis-signaling kinase 1 is a MAPKKK (mitogen-activated protein kinase) overexpressed in various types of human cancer including colorectal cancer. It mediates inflammation and apoptosis promotes cell proliferation through the transcription cyclin D1. 5-Fluorouracil remains one primary recommended drugs to manage However, this drug often causes adverse effects, notably diarrhea, vomiting, nausea, leukopenia. Therefore, novel treatment required eradicate these problems. The clinical implication apoptosis-signaling pathogenicity makes it an important target use natural compounds continues gain significant attention scientific community due their therapeutic efficacy. Method In study, computational models such as flexible docking, induced fit binding free energy calculation were employed identify small molecule inhibitors from known bioactive Spondias mombin reference 5-fluorouracil (Colorectal standard drug) targeting 1. Results Molecular docking studies identified 10 promising candidates which include uvaretin, rutin, isoquercitrin, ellagic acid, quercetin, linalool, acetyl eugenol, tangeretin (-)-catechin, d-sorbitol based on favorable affinity, with uvaretin having best score (− 11.328 kcal/mol). results further validated more dependable analysis calculation. These showed modest indices for ADMET parameters. dynamic simulation acid (-)-catechin greater stability leading compounds. Conclusion improved formed considerable stable interaction than 5-fluorouracil. They are non-carcinogenic. oral bioavailability toxicities obeyed Lipinski rule five. constructed quantitative structure–activity relationship model trustworthy R 2 coefficient value supports inhibition prowess findings research confer that could be considered potent inhibitors, confirmed experimentally lead

Language: Английский

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Impact of mutations on KAT6A enzyme and inhibitory potential of compounds from Withania somnifera using computational approaches

Computers in Biology and Medicine, Journal Year: 2025, Volume and Issue: 190, P. 110041 - 110041

Published: March 22, 2025

Language: Английский

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Targeting Conserved Regions of the SARS-CoV-2 Polymerase (RdRp) with Kinase Inhibitors as an Effective New Tactic for Discovering Dual-Action "Antiviral─Antiinflammatory" Drugs against COVID-19

Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108454 - 108454

Published: April 1, 2025

Language: Английский

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3‐arylcoumarins as the potential neuroprotective agents for the treatment of Alzheimer's disease by targeting monoamine oxidase: Molecular docking, 3D QSAR, and molecular dynamics simulations

Vietnam Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Abstract MAO‐A and MAO‐B have gathered pharmacological importance in Alzheimer's Parkinsons disease, owing to their function the monoamine neurotransmitters metabolism. The development of potent inhibitors is need hour. This research was aimed determine 3‐arylcoumarin scaffold's as enzyme inhibitor based on protein ligand interaction. density functional theory data confirmed that most compounds' derivatives were stable, validating properties. Molecular docking revealed potential molecular interaction between selected compounds targeted among which compound SC found be a MAO‐B. results investigation supported by MD simulations ADMET characteristics, demonstrated synthesized drug‐like qualities. Future could conducted significance field medicine.

Language: Английский

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In silico exploration of Aloe Vera leaf compounds as dual AChE and BChE inhibitors for Alzheimer’s disease therapy

Current Pharmaceutical Analysis, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Synthesis, DFT investigation, molecular docking, drug-likeness and molecular dynamic analysis of new quinoxaline-based pyrazoline derivatives

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 142405 - 142405

Published: April 1, 2025

Language: Английский

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Deciphering the in silico molecular mechanism of coumestrol activity for uterine fibroids remedy: a promising estrogenic target drug candidate

Journal of Biomolecular Structure and Dynamics, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 26

Published: April 17, 2025

Uterine fibroids (UF) are reproductive conditions that occur as tumours in the womb. It is a gynecological outgrowth of diverse sizes often allied with infertility risks might require surgery to reduce complication worst-case scenario women. Recent studies have uncovered estrogen can induce and facilitate other target pathways' action on cells for UF's pathogenesis, among targets probed pharmaceutical intervention. This study screens interaction effects 32 phytochemicals from indigenous adopted potent Chinese plants herbs; Chamomile, Pomegranate, Red clover, Cinnamomum, Date palm, against receptor alpha (ESRα) serve anti-UF drug candidates using silico tools through molecular mechanisms. The identifies coumestrol best-docked candidate (-9.6 kcal/mol) correlation binding free energy (-30.487 compared standard tamoxifen (-9.3 kcal/mol; -46.928 kcal/mol). downstream post-docking evaluation reveals excellent pharmacokinetics, drug-likeness, leadlikeness (no violation), less toxic (LD50; 2991 mg/kg), highly interactive ESRα. Coumestrol was top-ranked ESRα (1QKU) by PharmMapper 300 human protein targets, z-score 1.19368. density functional theory (DFT) dynamic simulation 200 ns reveal regions structure its complex contribute chemical reactivity, stability, flexibility, compactness druggability. Ultimately, emerged potential suitable management, therefore future direction application should be design synthesis new structural derivatives further silico, vitro, vivo studies.

Language: Английский

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