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The role of chlorine atom on the binding between acrylonitrile derivatives and fat mass and obesity‐associated protein
Author(s) -
Bai Ning,
Gan Ya,
Li Xitong,
Gao Shuting,
Yu Wenquan,
Wang Ruiyong,
Chang Junbiao
Publication year - 2021
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/jmr.2880
Subject(s) - acrylonitrile , cytotoxicity , chemistry , ic50 , chlorine atom , monomer , molecule , chlorine , fluorescence , fluorescence spectroscopy , in vitro , stereochemistry , combinatorial chemistry , medicinal chemistry , biochemistry , organic chemistry , physics , quantum mechanics , copolymer , polymer
In this work, seven acrylonitrile derivatives were selected as potential inhibitors of fat and obesity‐related proteins (FTO) by the aid of fluorescence spectroscopy, ultraviolet visible spectroscopy, molecular docking, and cytotoxicity methods. Results show that the interaction between 3‐amino‐2‐(4‐chlorophenyl)‐3‐phenylacrylonitrile ( 1a ) and FTO was the strongest among these derivatives. Thermodynamic analysis and molecular modeling show that the main force between 1a and FTO is hydrophobic interaction. The cytotoxicity test showed that the IC 50 value of 1a was 46.64 μmol/L, which indicated 1a had the smallest IC 50 value and had the best inhibitory effect on the proliferation of leukemia K562 cells among the seven derivatives. Both our previous results and this work show that chlorine atoms play important role in the binding of small molecules and FTO. This work brings new information for the study of FTO inhibitors.