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Synthesis and Biological Evaluation of 1,3,5‐Trisubstituted 2‐Pyrazolines as Novel Cyclooxygenase‐2 Inhibitors with Antiproliferative Activity
Author(s) -
Vahedpour Teymour,
Kaur Jatinder,
Hemmati Salar,
HamzehMivehroud Maryam,
Alizadeh Ali Akbar,
Wuest Frank,
Dastmalchi Siavoush
Publication year - 2021
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.202000832
Subject(s) - pharmacophore , chemistry , cyclooxygenase , stereochemistry , pyrazoline , enzyme , hydrogen bond , docking (animal) , in vitro , structure–activity relationship , combinatorial chemistry , biochemistry , medicinal chemistry , molecule , organic chemistry , medicine , nursing
A new series of 1,3,5‐trisubstituted 2‐pyrazolines for the inhibition of cyclooxygenase‐2 (COX‐2) were synthesized. The designed structures include a COX‐2 pharmacophore SO 2 CH 3 at the para ‐position of the phenyl ring located at C‐5 of a pyrazoline scaffold. The synthesized compounds were tested for in vitro COX‐1/COX‐2 inhibition and cell toxicity against human colorectal adenocarcinoma cell lines HT‐29. The lead compound (4‐chlorophenyl){5‐[4‐(methanesulfonyl)phenyl]‐3‐phenyl‐4,5‐dihydro‐1 H ‐pyrazol‐1‐yl}methanone ( 16 ) showed significant COX‐2 inhibition (IC 50 =0.05±0.01 μM), and antiproliferative activity (IC 50 =5.46±4.71 μM). Molecular docking studies showed that new pyrazoline‐based compounds interact via multiple hydrophobic and hydrogen‐bond interactions with key binding site residues of the COX‐2 enzyme.