Abstract
Acarbose and voglibose are well-known alpha-amylase inhibitors used for the management of type-II diabetes mellitus. Unfortunately, these well-known and clinically used inhibitors are also associated with several adverse effects. Therefore, there is still need to develop the safer therapy. Despite of a broad spectrum of biological significances of pyrazolone, it is infrequently evaluated for alpha-amylase inhibition. Current study deals with the synthesis and biological screening of aryl and arylidene substituted pyrazolones 1-18 for their potential alpha-amylase inhibitory activity. Structures of synthetic derivatives 1-18 were identified by different spectroscopic techniques. All compounds 1-18 (IC50 = 1.61 +/- 0.16 mu M to 2.38 +/- 0.09 mu M) exhibited significant to moderate inhibitory potential when compared to standard acarbose (IC50 = 1.46 +/- 0.26 mu M). A number of derivatives including 8-12 (IC50 = 1.68 +/- 0.1 mu M to 1.97 +/- 0.07 mu M) and 14-16 (IC50 = 1.61 +/- 0.16 mu M to 1.93 +/- 0.07 mu M) were found to be significantly active. Limited SAR suggested that different substitutions on compounds do not have any significant effect on the inhibitory potential. Compounds were found to be mixed-type inhibitors revealed by kinetic studies. However, in silico study was identified a number of key features participating in the interaction with the binding site of alpha-amylase enzyme. (C) 2018 Elsevier Masson SAS. All rights reserved.