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

AbstractIn 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.