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

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 1 HNMR, 13 C 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 IC 50 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.