Design, synthesis and evaluation of Coumarin-Phenylthiazole conjugates as cholinesterase inhibitors

Abstract

In this paper we report the design, synthesis, in-silico and in-vitro evaluations of a series of coumarin-phenylthiazole conjugates to inhibit cholinesterase enzymes. The coumarin and phenylthiazole derivatives were synthesized separately and further combined through covalent amine bond linkage. The compounds showed more inhibition towards BuChE than AChE. The compound, 4-(3-bromophenyl)-1,3-thiazol-2-amine exhibited the strongest inhibition against BuChE with an IC₅₀ value of 3.54 μM. For the conjugates, better inhibition activities towards BuChE are shown by 3-nitro, 3-bromo and 2-fluoro derivatives. It was also observed that the substitution at 3-position, on phenylthiazole produced better results against BuChE than 4-substituted counterparts.