Synthesis and Characterization of Thiazole Derivatives as Cholinesterase Inhibitors

ChemistrySelect, Год журнала: 2025, Номер 10(11)

Опубликована: Март 1, 2025

Abstract Fifteen new thiazole derivatives were synthesized and their cholinesterase inhibitory activities evaluated. The design of these compounds involves linking rings to a cyclopropyl moiety, followed by substitutions with various amine groups. structures the thiazole‐cyclopropyl confirmed using IR, HRMS, ¹H‐NMR, ¹ 3 C‐NMR, HPLC, single‐crystal X‐ray diffraction. Compounds 6g 6h found crystallize in monoclinic system space group P21/c , featuring α γ angles 90°. Cholinesterase inhibition was assessed Ellman method. While most exhibited weak effects on butyrylcholinesterase (BuChE), they showed significant acetylcholinesterase (AChE). Compound 6l potent AChE activity, an IC₅₀ 0.079 ± 0.16 µM, comparable Donepezil (IC₅₀ = 0.056 0.22 µM). Molecular docking, molecular dynamics simulations, MM/GBSA binding free energy calculations stable interactions between compound peripheral anionic site AChE. Furthermore, metal ion chelation studies demonstrated that as multitarget‐directed ligand, effectively chelated biologically relevant ions. In summary, shows potential inhibitor represents promising lead for further research development Alzheimer's disease treatment.

Язык: Английский

A Review of In Silico and In Vitro Approaches in the Fight Against Carbapenem‐Resistant Enterobacterales

Journal of Clinical Laboratory Analysis, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

ABSTRACT Objectives The rise in carbapenem‐resistant Enterobacterales (CRE) has reinforced the global quest for developing effective therapeutics. Traditional drug discovery approaches have been inadequate overcoming this challenge due to their resource and time constraints. Methods English literature was searched by structured queries related our review between January 1, 2020, December 31, 2024. Results key resistance mechanisms CRE, such as enzymatic hydrolysis, decreased permeability, efflux pump overexpression, examined review. Computational technologies become pivotal discovering novel antimicrobial agents with improved accuracy efficiency. Besides this, highlights advances structure‐ ligand‐based identifying potential drugs against CRE. Recent studies demonstrating use of silico techniques develop targeted CRE also explored. Moreover, underscores significance integrating both vitro counter Enterobacterales, supported latest studies. However, these promising computational a few major drawbacks, lack standardized parameterization, potentially false positives, complexity clinical translations. regulatory barriers restrict progress new antimicrobials market approval. Conclusion inhibitor is gaining popularity, it can be expedited refining them reliable validation. innovative hybrid need hour tackle mitigate threat resistance.

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