Antitumor Activities and Structure–Activity Relationship of Phosphotriester Derivatives of Homocamptothecin Based on a Semisynthetic Route
Yong-Qiang Zhang A E , Huo-Jun Zhang B E , Jing Zhang A , Juan Wang C , Jian-Zhong Yao A , Lin-Jian Zhu A , Chun-Lin Zhuang A , Sheng-Zheng Wang A , Guo-Qiang Dong A , Chun-Quan Sheng A D , Zhen-Yuan Miao A D and Wan-Nian Zhang A DA School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, P. R. China.
B Department of Radiology, Section of Oncologic Intervention, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, P. R. China.
C Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, P. R. China.
D Corresponding authors. Email: zhangwnk@hotmail.com; miaozhenyuan@hotmail.com; Shengcq@hotmail.com.
E These two authors contributed equally to this work.
Australian Journal of Chemistry 64(12) 1547-1553 https://doi.org/10.1071/CH11315
Submitted: 27 July 2011 Accepted: 9 September 2011 Published: 17 October 2011
Abstract
Based on a new semisynthetic route, a series of phosphotriester 7-alkyl-homocamptothecin derivatives are designed and synthesized. Cytotoxic activity assays show that compounds 12a and 14c with a methyl in position C7 of the homocamptothecin are more potent than the other derivatives and the positive drug irinotecan against A-549, MCF-7, and LOVO cell lines. Moreover, compound 14c shows potent tumour inhibitory activity in a Colo205 xenograft model.
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