Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents.
Two series of pyrazole derivatives designing for potential EGFR kinase inhibitors have been discovered. Some of them exhibited significant EGFR inhibitory activity. Compound 3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide (C5) displayed the most potent EGFR inhibitory activity with IC₅₀ of 0.07 μM, which was comparable to the positive control erlotinib. Docking simulation was performed to position compound C5 into the EGFR active site to determine the probable binding model. Antiproliferative assay results indicating that some of the pyrazole derivatives own high antiproliferative activity against MCF-7. Compound C5 showed significant antiproliferative activity against MCF-7 with IC₅₀ of 0.08 μM. Therefore, compound C5 with potent inhibitory activity in tumor growth inhibition would be a potential anticancer agent.
Lv
Peng-Cheng
PC
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Li
Huan-Qiu
HQ
Sun
Juan
J
Zhou
Yang
Y
Zhu
Hai-Liang
HL
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013854:Thioamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D013890:Thiourea / Q000737:chemistry*
C559230:3-(3,4-dimethylphenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide; D000970:Antineoplastic Agents; D011720:Pyrazoles; D013854:Thioamides; C031280:pyrazole; D066246:ErbB Receptors; D013890:Thiourea