Meeting organometallic chemistry with drug discovery: C-H activation enabled discovery of a new ring system of 12H-Indazolo[2,1-a]cinnolin-12-ones with anti-proliferation activity

doi:10.1016/j.bmcl.2019.126916

	Meeting organometallic chemistry with drug discovery: C-H activation enabled discovery of a new ring system of 12H-Indazolo[2,1-a]cinnolin-12-ones with anti-proliferation activity
	Zhang, Xiang 1; Bai, Ruisong 2,3; Xiong, Huan4 ; Xu, Hongtao4 ; Hou, Wei 2,3
	2020-02-15
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN	0960-894X
EISSN	1464-3405
卷号	30 期号:4
发表状态	已发表
DOI	10.1016/j.bmcl.2019.126916
摘要	A diverse library of new ring system 12H-indazolo[2,1-a]cinnolin-12-ones have been synthesized efficiently via Ru (II) and Rh (III) catalyzed tandem C-H alkylation/[4 + 2] annulation with diazo compounds in high to excellent yields. For the first time, we evaluated the biological activity of these compounds with this new skeleton and found some compounds exhibited high cytotoxic activity against human PC-3 and PANC-1 tumor cell lines with nanomolar IC50. Among them, the most potent compound 36 showed broad-spectrum cytotoxic activities against a series of human tumor cell lines derived from different organs (IC50 similar to 41 to 197 nM). Moreover, preliminary mechanistic studies indicated that 36 could inhibit the colony formation, cause cell cycle arrest and induce apoptosis of PC-3 cancer cells in a dose-dependent manner. Further intracellular mechanisms investigation found that 36 treatments could dose-dependently decrease the levels of caspase-3 and PARP and up-regulate the level of cleaved PARP. These results suggested that 36 is a novel compound with good potential in the treatment of human cancers and worthy of further investigation.
关键词	C-H activation New heterocyclic skeleton Molecular hybridization Anti-cancer Apoptosis
收录类别	SCI ; SCIE ; IC
语种	英语
资助项目	China Postdoctoral Science Foundation[2017M612024]
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
WOS类目	Chemistry, Medicinal ; Chemistry, Organic
WOS记录号	WOS:000507987200027
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS关键词	BIOLOGICAL EVALUATION ; ANTICANCER AGENTS ; DERIVATIVES ; IDENTIFICATION ; STRATEGY ; ANILINES ; DESIGN ; ACCESS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/105296
专题	免疫化学研究所_特聘教授组_功能筛选实验室免疫化学研究所_特聘教授组_抗体设计学实验室
通讯作者	Zhang, Xiang; Xu, Hongtao; Hou, Wei
作者单位	1.Zhengzhou Univ, Dept Pharm, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China 2.Zhejiang Univ Technol, Coll Pharmaceut Sci, Hangzhou 310014, Peoples R China 3.Zhejiang Univ Technol, IDD&CB, Hangzhou 310014, Peoples R China 4.ShanghaiTech Univ, SIAIS, Shanghai, Peoples R China
通讯作者单位	上海科技大学
推荐引用方式 GB/T 7714	Zhang, Xiang,Bai, Ruisong,Xiong, Huan,et al. Meeting organometallic chemistry with drug discovery: C-H activation enabled discovery of a new ring system of 12H-Indazolo[2,1-a]cinnolin-12-ones with anti-proliferation activity[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2020,30(4).
APA	Zhang, Xiang,Bai, Ruisong,Xiong, Huan,Xu, Hongtao,&Hou, Wei.(2020).Meeting organometallic chemistry with drug discovery: C-H activation enabled discovery of a new ring system of 12H-Indazolo[2,1-a]cinnolin-12-ones with anti-proliferation activity.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,30(4).
MLA	Zhang, Xiang,et al."Meeting organometallic chemistry with drug discovery: C-H activation enabled discovery of a new ring system of 12H-Indazolo[2,1-a]cinnolin-12-ones with anti-proliferation activity".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 30.4(2020).