Design, syntheses and antitumor activities evaluation of 1,5‐diaryl substituted pyrazole secnidazole ester derivatives

• Published in: Journal of heterocyclic chemistry Vol. 58; no. 8; pp. 1656 - 1664
• Main Authors: Teng, Qing‐Hu, Sun, Gui‐Xia, Luo, Shu‐Ying, Wang, Kai, Liang, Fu‐Pei
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Inc 01.08.2021; Wiley; Wiley Subscription Services, Inc
• Subjects: Anticancer properties; Apoptosis; Carboxylic acids; Cell cycle; Chemistry; Chemistry, Organic; Cycle ratio; Liver; Mitochondria; Physical Sciences; Pyrazole; Science & Technology; Substitutes; DRUG CANDIDATE; CELLS; POTENT; ACID; COX-2; DUAL INHIBITORS; DISCOVERY
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.4302

According to the drug hybridization principle, a series of novel 1,5‐diaryl substituted pyrazole secnidazole ester derivatives (6aa–6gc) have been synthesized by the combinations of various 1,5‐diarylpyrazole‐3‐carboxylic acids with secnidazole. The in vitro antitumor/cytotoxicities activities against tumor and normal cell lines, including NCI‐H460 (lung tumor cell), MCG‐803 (gastric tumor cell), Skov‐3 (ovarian tumor cell), BEL‐7404 (liver tumor cell) and HL‐7702 (normal liver cell), have been evaluated using MTT assay. All compounds showed promising inhibitory activities against four tumor cell lines. The IC50 of 6bc against the BEL‐7404 cell was 2.03 μM, and those of 6fc against the NCI‐H460, MCG‐803 and Skov‐3 were 1.34, 0.14, and 0.87 μM, respectively. All these values were much lower than those of the cisplatin. Furthermore, 6fc and 6bc were also verified to be considerably safe for normal human liver cell, since the lower IC50 values than cisplatin. Based on these results, the cell cycle analysis, apoptosis ratio detection and mitochondrial membrane potential assay of 6fc and 6bc were further performed aiming to investigate their inhibition mechanism of BEL‐7404 cells. It is revealed that they have effectively inhibited the cell growth by arresting the BEL‐7404 cells at S phase and induced apoptosis through the mitochondria‐mediated pathway.