Synthesis and biological evaluation of novel cabazitaxel analogues

doi:10.1016/j.bmc.2021.116224

	Synthesis and biological evaluation of novel cabazitaxel analogues
	Ren, Sumei 1,2; Zhang, Minmin 3; Wang, Yujie 1; Guo, Jia 1; Wang, Junfei 1; Li, Yingxia 1; Ding, Ning 1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY
	2021-07-01
卷号	41 页码:12
关键词	Tritium extraction Hydrogen isotopes Eutectic Pb-Li Fusion fuel cycle Cabazitaxel Docetaxel Taxel Anticancer Semi-synthesis 10-Deacetylbaccatin III Cytotoxicity
ISSN号	0968-0896
DOI	10.1016/j.bmc.2021.116224
通讯作者	Ding, Ning(dingning@fudan.edu.cn)
英文摘要	Cabazitaxel is one of the most recently FDA-approved taxane anticancer agent. In view of the advantages in preclinical and clinical data of cabazitaxel over former toxoids, the synthesis and biological evaluation of novel cabazitaxel analogues were conducted. First, a novel semi-synthesis of cabazitaxel was described. This strategy is concise and efficient, which needs five steps from the 10-deacetylbaccatin III (10-DAB) moiety and a commercially available C13 side chain precursor with a 32% overall yield. Besides, this strategy avoids using many hazardous reagents that involved in the previously reported processes. Then, a panel of cabazitaxel analogues were prepared basing on this strategy. The cytotoxicity evaluations showed that the majority of these cabazitaxel analogues are potent against both A549 and KB cells and their corresponding drug-resistant cell lines KB/VCR, and A549/T, respectively. Further in vivo antitumor efficacies assessment of 7,10-di-O-methylthiomethyl (MTM) modified cabazitaxel (compounds 16 and 19) on SCID mice A549 xenograft model showed they both had similar antitumor activity to the cabazitaxel. Since compound 19 was observed causing more body wight loss on the mice than 16, these preliminary studies suggest 16 might be a potent drug candidate for further preclinical evaluation.
资助项目	National Major Scientific and Technological Special Project of China for Significant New Drugs Development[2018ZX09101004-003] ; National Major Scientific and Technological Special Project of China for Significant New Drugs Development[2018ZX09101-004-006-008]
WOS关键词	BETA-LACTAMS ; TAXANE ; PACLITAXEL ; TAXOIDS ; DESIGN
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000661664000009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297183]
专题	中国科学院上海药物研究所
通讯作者	Ding, Ning
作者单位	1.Fudan Univ, Sch Pharm, Dept Med Chem, Shanghai 201203, Peoples R China 2.Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518060, Guangdong, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Ren, Sumei,Zhang, Minmin,Wang, Yujie,et al. Synthesis and biological evaluation of novel cabazitaxel analogues[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2021,41:12.
APA	Ren, Sumei.,Zhang, Minmin.,Wang, Yujie.,Guo, Jia.,Wang, Junfei.,...&Ding, Ning.(2021).Synthesis and biological evaluation of novel cabazitaxel analogues.BIOORGANIC & MEDICINAL CHEMISTRY,41,12.
MLA	Ren, Sumei,et al."Synthesis and biological evaluation of novel cabazitaxel analogues".BIOORGANIC & MEDICINAL CHEMISTRY 41(2021):12.