Hussain_2022_Chem.Biodivers__

A series of twenty bis -thiazolidinone based chalcone scaffolds (1-20) were synthesized and characterized by using various spectroscopic tools such as HR-EI-MS, 1 HNMR, 13 CNMR and were screened in vitro for their AChE and BuChE inhibition profile. It was noteworthy, that all the synthetic analogues (except analogues 10, 12 and 1 4 , which are found to be inactive) showed moderate to good inhibitory potentials on screening against AchE and BuChE enzymes with IC 50 values ranging from 0.10 +/-0.050 to 7.60 +/- 0.10 microM and 0.10 +/- 0.050microM to 10.70 +/- 0.20 microM as compared to standard Donepezil inhibitor (IC 50 = 0.016 +/- 0.12 microM), (IC 50 = 4.5 +/- 0.11 microM). Among the current series, analogue 20 (IC 50 = 0.10 +/- 0.050microM), (IC 50 = 0.10 +/- 0.050microM) bearing trihydroxy substitutions on ortho -, meta - and para -position of both rings A and B , respectively was found to be the most active inhibitor of AChE and BuChE enzymes . Analogue 19 (IC 50 = 0.20 +/- 0.050 microM), (IC 50 = 0.20 +/- 0.050microM) bearing dihydroxy substitutions on ortho - and meta -position of both ring A and ring B respectively, was identified as the second most potent inhibitor against both these enzymes. Potent analogs were further subjected to molecular docking study to identify the binding interactions with enzymes active site. SAR study was done for all the analogues mostly based on substitution pattern on both ring A and B respectively.