Hierarchical Virtual Screening of SARS-CoV-2 Main Protease Potential Inhibitors: Similarity Search, Pharmacophore Modeling, and Molecular Docking Study

Anti-Infective Agents, Год журнала: 2024, Номер 22(4)

Опубликована: Фев. 2, 2024

Background: The outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) resulted in a widespread pandemic. Various approaches involved the repositioning antiviral remedies and other medications. Several therapies, including oral treatments, represent some to adapting long existence In silico studies provide valuable insights throughout drug discovery development compliance with global efforts overcome main protease is an essential target viral cycle. Computer-aided design accelerates identification potential therapy. Aims: This work aims identify SARS-CoV-2 inhibitors using different aspects approaches. Methods: this work, we conducted hierarchical virtual screening inhibitors. A similarity search was screen molecules similar inhibitor PF-07321332. Concurrently, structure-based pharmacophores, besides ligand-based were derived. drug-likeness filter filtered compounds retrieved from pharmacophore modeling before being subjected molecular docking. candidate that showed higher affinity than reference further absorption, distribution, metabolism, excretion (ADME) parameters. Results: According binding ADME analysis, four (CHEMBL218022, PubChem163362029, PubChem166149100, PubChem 162396459) prioritized as promising hits. above not reported before; no previous experimental bioactive assays are available. Conclusion: Our time-saving approach represents strategy for discovering novel SARS-CoV- 2 ultimate hits may be nominated leads

Язык: Английский

UNRAVELLING THE INTERACTION BETWEEN GARCINISIDONE-A AND HER2 PROTEIN IN BREAST CANCER: A COMPUTATIONAL STUDY

International Journal of Applied Pharmaceutics, Год журнала: 2024, Номер unknown, С. 99 - 104

Опубликована: Фев. 15, 2024

Objective: One substance found in the leaves of Garcinia cowa Roxb that has anticancer properties is garcinisidone-A. The study aims to simulate docking garcinisidone-A (Gar-A), molecular dynamics, and predict ADME by predicting binding HER2 protein breast cancer cells developing new drug candidate options for treatment, often starting with computational analysis. Methods: research method involves utilization pkCSM applications, Gar-A simulation using Gnina software version 1.0.2, dynamics conducted GROMACS 2022.2 CHARMMGUI applications. Results: a weight less than 500, Log P value greater 5, limited amount water solubility, low level skin permeability, good intestinal Convolutional Neural Network (CNN) pose score on 0.6178. It also does not readily cross blood-brain barrier, total clearance values indicate rapid elimination via other excretory routes or enzyme metabolism. thought have interactions HER2. There are hydrogen bond amino acids Lys753 Asp863, carbon-hydrogen bonds Leu785, Ser783, Thr862, alkyl Leu726, Leu852, Ile767. stability Gar-A-substrate interaction could been more evident during 100 ns simulation. Conclusion: physicochemical align Lipinski's rule candidates. predictions permeability Gar-A; however, it suggests cannot penetrate barrier. results reveal close one which indicates similar action its natural ligand simulations stable. illustrate potential as anticancer.

Язык: Английский

Design, Synthesis, Anti-Proliferative and Molecular Docking Studies of Combretastatin A4 Analogues with 2-Azetidinone Moiety

Опубликована: Янв. 1, 2024

Series of 2-azetidinones have been designed as combretastatin A4 analogues with two substituted phenyl rings connected by a bridge composed amidic carbonyl and β-lactam ring. The target compounds (7 – 11, 20 23 21 31) synthesized characterized FT-IR, 1H NMR, 13C NMR mass spectrometry. anti-proliferative activity the was investigated studying their effect on viability breast cancer cell line MCF-7 normal WRL‑68. In terms IC50 values, 9 21, were found to be most potent values 34.27 28.86 µM for respectively. Compounds subjected detailed molecular docking studies, optimized structures docked colchicine binding site in tubulin (PDB ID: 4O2B), obtained results indicated that these can act antitubulin agents excellent scores site.

Язык: Английский