Synthesis of Benzothiazole Linked Triazole Conjugates and Their Evaluation Against Cholinesterase Enzymes

Abstract

In this paper we report the synthesis, in‐silico and in‐vitro evaluations of a new series of benzothiazole linked triazole conjugates. The synthesized compounds have been evaluated as the inhibitor of cholinesterase enzymes using Ellman's method. The benzothiazole and triazole derivatives were synthesized separately and further combined through covalent amide bond linkage.The compounds showed good to excellent results towards butyryl cholinesterase (BuChE) inhibition. Docking studies revealed that the hydrophobic aromatic part of N‐benzothiazole binds to the PAS and the 1,2,4‐triazole residue binds to the CAS of BuChE. The in‐silico docking results for BuChE are consistent with the in‐vitro results. Also, the molecular dynamics simulation studies of the best docked molecule 8 a had shown similar binding stability as the reference drug donepezil. Good molecular interaction was also observed for acetylcholinesterase (AChE). The molecular modelling and evaluations against cholinesterase enzyme provided novel lead molecule which with further modifications in their structure have potential for the treatment of Alzheimer disease (AD) in future.

Screening of Multitarget-Directed Natural Compounds as Drug Candidates for Alzheimer’s Disease Using In Silico Techniques: Their Extraction and In Vitro Validation

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Crystal structure, quantum chemical insights, and molecular docking studies of Naryl-2-(N-disubstituted) acetamide compounds: potential inhibitors for neurodegenerative enzymes

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