Synthesis and biological evaluation of 7-alkenyl homocamptothecins as potent topoisomerase I inhibitors.
Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven-membered β-hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7-alkenyl-homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A-549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I-inhibition activity.
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.
Lingjian
L
Zhu
Xianghua
X
Zhang
Ning
N
Lei
Wenfeng
W
Liu
Zhenyuan
Z
Miao
Chunlin
C
Zhuang
Chunquan
C
Sheng
Wei
W
Guo
Guoqiang
G
Dong
Jianzhong
J
Yao
Pengfei
P
Cheng
Wannian
W
Zhang
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D053837:DNA Cleavage; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D019772:Topotecan / Q000633:toxicity
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D004247:DNA; C120029:homocamptothecin; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin