Synthesis and In Vitro Antitumor Activity of Novel Bivalent -Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

doi:10.3390/ijms19103179

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	Synthesis and In Vitro Antitumor Activity of Novel Bivalent -Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target
	Gu, Hongling 2; Li, Na 2; Dai, Jiangkun 2; Xi, Yaxi 2; Wang, Shijun 2; Wang, Junru 1,2
刊名	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
	2018-10
卷号	19 期号:10
关键词	bivalent -carbolines antitumor apoptosis DNA-binding affinity bcl-2
ISSN号	1422-0067
DOI	10.3390/ijms19103179
文献子类	Article
英文摘要	A series of novel bivalent -carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent -carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C-3 position could enhance the antitumor activity of -carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with -carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation.
资助项目	National Natural Science Foundation of China[81773603] ; Open Foundation of Key Laboratory of Synthetic and National Foundation Molecule Chemistry of the Ministry of Education (Northwest University, China)[00000000] ; State Key Laboratory of Drug Research[SIMM1705KF-09] ; National Training Program on Undergraduate Innovation and Entrepreneurship (Northwest A&F University, China)[201803018]
WOS关键词	BETA-CARBOLINE DERIVATIVES ; TOPOISOMERASE-II INHIBITORS ; BIOLOGICAL EVALUATION ; HARMINE DERIVATIVES ; ANTICANCER AGENTS ; BIFUNCTIONAL INTERCALATORS ; BINDING PROPERTIES ; OXIDATIVE STRESS ; DESIGN ; APOPTOSIS
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000448951000334
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279552]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Wang, Junru
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China 2.Northwest A&F Univ, Coll Chem & Pharm, 22 Xinong Rd, Yangling 712100, Shaanxi, Peoples R China;
推荐引用方式 GB/T 7714	Gu, Hongling,Li, Na,Dai, Jiangkun,et al. Synthesis and In Vitro Antitumor Activity of Novel Bivalent -Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2018,19(10).
APA	Gu, Hongling,Li, Na,Dai, Jiangkun,Xi, Yaxi,Wang, Shijun,&Wang, Junru.(2018).Synthesis and In Vitro Antitumor Activity of Novel Bivalent -Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,19(10).
MLA	Gu, Hongling,et al."Synthesis and In Vitro Antitumor Activity of Novel Bivalent -Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 19.10(2018).