Hybrids of Thiazolidin-4-Ones and 1,3,4-Thiadiazole: Synthesis and Biological Screening of A Potential New Class of Acetylcholinesterae Inhibitors

Abstract

Using propanoic acid and thiosemicarbazide as starting materials, a new sequence of thiazolidin-4-one analogs with thiadiazole derivative was synthesized in appreciable yield. Spectral techniques such as IR, 1H NMR, 13C NMR, and MS were used to validate the structures of the synthesized compounds (4a-t). In vitro acetylcholinesterase inhibitory activity of these synthesized compounds was assessed using an Ellman's method spectrophotometer and donepezil as a standard drug. Compounds 2-((5-ethyl-1,3,4-thiadiazol-2-yl)imino)-5-(4-methylbenzylidene)thiazolidin-4-one(4o) and 5-(4-(benzyloxy)benzylidene)-2-((5-ethyl-1,3,4-thiadiazol-2-yl)imino)thiazolidin-4-one(4i) were found to be potent AChE enzyme inhibitors, with pIC50 (mM) values of 1.30±0.007 and 1.22±0.002, respectively. Finally, these significant results could pave the way for the development of new AChE inhibitors and will serve as the basis for future research.