The future of pharmaceuticals: Artificial intelligence in drug discovery and development

Journal of Pharmaceutical Analysis, Год журнала: 2025, Номер unknown, С. 101248 - 101248

Опубликована: Фев. 1, 2025

Язык: Английский

Bis(7)-harmine derivatives as potential multi-target anti-Alzheimer agents

Frontiers in Chemistry, Год журнала: 2025, Номер 13

Опубликована: Янв. 29, 2025

Introduction The multi-targeted ligands (MTDL) strategy has been recognized as a promising Approach for the development of effective treatments against Alzheimer’s disease (AD), due to presence multiple pathological mechanisms in AD. In this study, series bis(7)-harmine derivatives were designed and synthesized multifunctional drugs treatment Methods by chemical methods their structure was confirmed nuclear magnetic resonance (NMR). Ellman’s assay utilized assess inhibitory potential h AChE BuChE. activity these on both MAO-A MAO-B assessed using fluorescence-based method. thioflavin T (Th-T) fluorescence used inhibition A β 1−42 self-aggregation. cytotoxicity evaluated MTT assay. Surflex-Dock program Sybyl-X2.0 Software employed molecular docking. Results vitro studies revealed that numerous compounds exhibited potent AChE, (IC 50 < 1 μM), well aggregation 20 μM). Importantly, multitarget 6d , 8c 8d remarkable efficacy simultaneously mitigating -induced toxicity SH−SY5Y cells while demonstrating minimal cytotoxicity. Furthermore, predicted ADMET results suggested possessed favorable pharmacokinetic properties demonstrated low levels. Additionally, docking within activesites MAO-B, elucidated mechanism. Discussion conclusion Based findings, it is evident hold multi-functional AD treatment.

Язык: Английский

Natural phenol carbamates: Selective BuChE/FAAH dual inhibitors show neuroprotection in an Alzheimer’s disease mouse model

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 281, С. 117003 - 117003

Опубликована: Окт. 30, 2024

Язык: Английский