Design and biological evaluation of novel hybrids of 1, 5-diarylpyrazole and Chrysin for selective COX-2 inhibition

Bioorg Med Chem. 2018 Aug 7;26(14):4264-4275. doi: 10.1016/j.bmc.2018.07.022.

Shen-Zhen Ren ¹, Zhong-Chang Wang ¹, Xiao-Hua Zhu ¹, Dan Zhu ¹, Zhang Li ¹, Fa-Qian Shen ¹, Yong-Tao Duan ², Han Cao ¹, Jing Zhao ³, Hai-Liang Zhu ⁴

Affiliations

1 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, PR China.
2 Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Zhengzhou Children's Hospital, Zhengzhou 450018, PR China.
3 State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210023, PR China.
4 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, PR China. Electronic address: zhuhl@nju.edu.cn.

PMID: 30031652 DOI: 10.1016/j.bmc.2018.07.022

Abstract

The overexpress of COX-2 was clearly associated with carcinogenesis and COX-2 as a possible target has long been exploited for Cancer therapy. In this work, we described the design and synthesis of a series of diarylpyrazole derivatives integrating with chrysin. Among them, compound e9 exhibited the most potent inhibitory activity against COX-2 and antiproliferative activity against Hela cells with IC₅₀ value of 1.12 μM. Further investigation revealed that e9 could induce Apoptosis of Hela cells by mitochondrial depolarization and block the G1 phase of cell cycle in a dose-dependent manner. Besides, molecular docking simulation results was further confirmed that e9 could bind well with COX-2. In summary, compound e9 may be promising candidates for Cancer therapy.

Keywords

Antiproliferative; COX-2 inhibitor; Chysin; Docking; Pyrazole.

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