α-Glucosidase, α-Amylase Inhibition, Kinetics and Docking Studies of Novel (2-Chloro-6-(trifluoromethyl)benzyloxy)arylidene) Based Rhodanine and Rhodanine Acetic Acid Derivatives

Abstract

In our effort to identify potent fluorinated small molecules as antidiabetic compounds, a novel fluorinated series of 2-chloro-6-(trifluoromethyl)benzyloxy arylidene derived Rhodanine and Rhodanine-acetic acid derivatives were synthesized and screened for α-glucosidase and α-amylase inhibitory activity. Newly synthesized compounds were characterized by 1HNMR, 13C NMR, and LCMS spectral data. Among the tested compounds, (Z)-5-(4-(2-chloro-6-(trifluoromethyl)benzyloxy)benzylidene)-2-thioxothiazolidin-4-one(5 a) and 2-((Z)-5-(4-(2-chloro-6-(trifluoromethyl)benzyloxy)benzylidene)-4-oxo-2-thioxothiazoli-din-3-yl)acetic acid(6 a) emerged as most promising α-glucosidase inhibitors with IC50 values 4.76±0.64 μM and 4.91±0.45 μM, respectively. Further, the kinetic inhibition experiments against yeast α-glucosidase for compounds 5 a and 6 a indicated that these are competitive inhibitors with inhibitory constant (Ki) 0.54 μg and 1.15 μg respectively. Molecular docking studies on α-glucosidase was performed by homology modelingfor the most potent compounds 5 a and 6 a to understand the putative binding mode. The study revealed substantial binding of the compounds to the active site of α-glucosidase, indicating that the position of the substituent plays a key role in its inhibitory potential.