Synthesis, biological evaluation and molecular modeling of dihydro-pyrazolyl-thiazolinone derivatives as potential COX-2 inhibitors.
A series of dihydro-pyrazolyl-thiazolinone derivatives (5a-5t) have been synthesized and their biological activities were also evaluated as potential cyclooxygenase-2 (COX-2) inhibitors. Among these compounds, compound 2-(3-(3,4-dimethylphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (5a) displayed the most potent COX-2 inhibitory activity with IC(50) of 0.5μM, but weak to COX-1. Docking simulation was performed to position compound 5a into the COX-2 active site to determine the probable binding model. Based on the preliminary results, compound 5a with potent inhibitory activity and low toxicity would be a potential and selective anti-cyclooxygenase-2 agent.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, PR China.
Ke-Ming
KM
Qiu
Ru
R
Yan
Man
M
Xing
Hai-Hong
HH
Wang
Hong-En
HE
Cui
Hai-Bin
HB
Gong
Hai-Liang
HL
Zhu
D000818:Animals; D001665:Binding Sites; D020134:Catalytic Domain; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
C578972:2-(3-(3,4-dimethylphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013844:Thiazoles; C031280:pyrazole; D051546:Cyclooxygenase 2