Isatin-linked 4,4-dimethyl-5-methylene-4,5-dihydrothiazole-2-thiols for inhibition of acetylcholinesterase

A series of novel isatin-linked 4,4-dimethyl-5-methylene-4,5-dihydrothiazole-2-thiols (IT2Ts) 1a–1g were designed as acetylcholinesterase (AChE) inhibitors capable interacting with both the catalytic active site (CAS) and peripheral anionic (PAS) enzyme simultaneously. The target IT2Ts prepared through a short synthesis in moderate yield. most potent this 1b 1c (IC50 = 18.2 27.5 μM, respectively) outperformed rivastigmine comparable to galantamine, clinically used AChE inhibitors. Furthermore, displayed non-competitive inhibition patterns kinetic studies, whereas molecular modeling predicted simultaneous interaction CAS PAS. In silico methods several promising drug-like characteristics 1b. Taken together, these results indicate warrants further investigation multitarget-directed ligand for inhibition.