Design, synthesis, and anticancer evaluation of nitrobenzoxadiazole-piperazine hybrids as potent pro-apoptotic agents

被引：4

作者：

Chen, Yiliang ^{[1
]}

Pan, Wenwen ^{[1
]}

Ding, Xiaolong ^{[1
]}

Zhang, Liang ^{[1
]}

Xia, Qinfei ^{[1
]}

Wang, Qi ^{[1
]}

Chen, Qian ^{[1
]}

Gao, Qinghe ^{[2
]}

Yan, Jufen ^{[1
]}

Lesyk, Roman ^{[3
]}

Tang, Zilong ^{[4
]}

Han, Xinya ^{[1
]}

机构：

[1] Anhui Univ Technol, Sch Chem & Chem Engn, Maanshan 243032, Anhui, Peoples R China

[2] Xinxiang Med Univ, Sch Pharm, Xinxiang 453003, Henan, Peoples R China

[3] Danylo Halytsky Lviv Natl Med Univ, Dept Pharmaceut Organ & Bioorgan Chem, Pekarska 69, UA-79010 Lvov, Ukraine

[4] Hunan Univ Sci & Technol, Minist Educ, Key Lab Theoret Organ Chem & Funct Mol, Xiangtan 411201, Hunan, Peoples R China

来源：

TETRAHEDRON | 2023年 / 138卷

基金：

中国国家自然科学基金;

关键词：

7-Nitrobenzo[c][1; 2; 5]Oxadiazole; Piperazine; Anticancer; Apoptosis; S-TRANSFERASE INHIBITOR; 6-(7-NITRO-2,1,3-BENZOXADIAZOL-4-YLTHIO)HEXANOL NBDHEX; BIOLOGICAL EVALUATION; TUMOR-CELLS; DERIVATIVES; GROWTH; RESISTANCE; ANTIBACTERIAL; SENSITIVITY; ANTAGONIST;

D O I：

10.1016/j.tet.2023.133393

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Inspired by antitumor drug 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX), a series of novel nitrobenzoxadiazole-piperazine hybrids were designed, synthesized, and evaluated for their anticancer activities in vitro. The representative hybrids 3u, 3v, and 3w containing a chloromethyl substitution exhibited the most potent anticancer effects against MCF-7, HepG2, and A549 cells. Among the syn-thesized compounds, 3u was found to be the most active derivative possessing broad-spectrum cyto-toxicity against HepG2 and A549 cells with the highest IC50 values of 3.50 and 4.73 mM, respectively. Mechanistic studies of anti-proliferative activity revealed that compound 3u triggered apoptosis in cancer cell lines through hydrolyzing of PARP by caspase 3, and effectively inhibited colony formation. These results suggested that compound 3u deserves further development as a promising lead compound for discovering novel antitumor agents.(c) 2023 Elsevier Ltd. All rights reserved.

引用

页数：11

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