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

Souad J. Laftaa,

Asim A. Balakit,

Nabel B. Ayrim

и другие.

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

Identification of Potent Acetylcholinesterase Inhibitors as New Candidates for Alzheimer Disease via Virtual Screening, Molecular Docking, Dynamic Simulation, and Molecular Mechanics–Poisson–Boltzmann Surface Area Calculations DOI Creative Commons
Hind Yassmine Chennai, Salah Belaıdı, Lotfi Bourougaa

и другие.

Molecules, Год журнала: 2024, Номер 29(6), С. 1232 - 1232

Опубликована: Март 10, 2024

Huperzine A (HUP) plays a crucial role in Alzheimer’s therapy by enhancing cognitive function through increased cholinergic activity as reversible acetylcholinesterase (AChE) inhibitor. Despite some limitations being seen AChE inhibitors, ongoing research remains dedicated to finding innovative and more effective treatments for disease. To achieve the goal of discovery potential HUP analogues with improved physicochemical properties, less toxic high biological activity, many silico methods were applied. Based on acetylcholinesterase–ligand complex, an e-pharmacophore model was developed. Subsequently, virtual screening involving collection 1762 natural compounds, sourced from PubChem database, performed. This yielded 131 compounds that exhibited compatibility established pharmacophoric hypothesis. These selected ligands then subjected molecular docking within active site 4EY5 receptor. As result, we identified four displayed remarkable scores low free binding energy target. top CID_162895946, CID_44461278, CID_44285285, CID_81108419, submitted ADMET prediction dynamic simulations, yielding encouraging findings terms their pharmacokinetic characteristics stability. Finally, simulation, cross-dynamic correlation matrix, landscape, MM-PBSA calculations demonstrated two formed very resilient complexes enzyme acetylcholinesterase, significant affinity. Therefore, these are recommended further experimental possible inhibitors.

Язык: Английский

Процитировано

10
Synthesis, Antioxidant, and Antidiabetic Potential of Ferrocenylmethylnucleobase Compounds: In Vitro, In Silico Molecular Docking, DFT Calculation, and Molecular Dynamic Simulations DOI Open Access
Aicha Adaika, Yahia Bekkar, Souhir Youmbai

и другие.

Applied Organometallic Chemistry, Год журнала: 2025, Номер 39(2)

Опубликована: Янв. 12, 2025

ABSTRACT This study presents the synthesis and characterization of a novel series ferrocenylmethylnucleobase compounds, namely, FcMeAd, FcMeCy, FcMeTh, (FcMe)₂Ad with promising antioxidant antidiabetic properties. Spectroscopic techniques confirmed their sandwich‐like geometry, nucleobase moiety coordinated to ferrocene unit. Density functional theory (DFT) optimization revealed alignment existing crystallographic data indicated low frontier molecular orbital (FMO) energy gaps, suggesting facile intramolecular charge transfer potential biological activity. The activity was evaluated in vitro through inhibition assays targeting α‐glucosidase α‐amylase enzymes, which supported by silico docking studies. Among FcMeTh exhibited highest properties due presence carbonyl amide functionalities, along an electron‐donating methyl group. Molecular dynamics (MD) simulations high binding affinity structural stability docked strong interactions target further validating these compounds as effective inhibitors. Pharmacokinetic ADMET evaluations nontoxic, noncarcinogenic nature suitability for oral administration. combined findings, including critical insights from MD simulations, suggest that especially possess enhanced highlights therapeutic agents managing oxidative stress Type 2 diabetes.

Язык: Английский

Процитировано

1
Clinical informatics and molecular hybridization of established clinical DPP-4 inhibitors to generate next-level diabetes type 2 drugs DOI
Lotfi Bourougaa, Mebarka Ouassaf, Bader Y. Alhatlani

и другие.

Chemical Papers, Год журнала: 2024, Номер unknown

Опубликована: Сен. 20, 2024

Язык: Английский

Процитировано

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

Souad J. Laftaa,

Asim A. Balakit,

Nabel B. Ayrim

и другие.

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

Процитировано

0