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

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, H-1 NMR, C-13 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 pIC(50) (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.