Abstract
A series of novel alkyl amine-substituted icariside II (ICA II) derivatives were synthesized by Mannich reactions at the 6-C position (compounds 4a⁻d) and changing the carbon chain length at the 7-OH position (compounds 7a⁻h), and their in vitro antitumor activity towards human breast cancer lines (MCF-7 and MDA-MB-231) and human hepatoma cell lines (HepG2 and HCCLM3-LUC) were evaluated by the MTT assay. Compared with ICA II, most of the twelve derivatives showed good micromole level activity and a preliminary structure-activity relationship (SAR) for the anticancer activity was obtained. Compound 7g showed the most potent inhibitory activity for the four cancer cell lines (13.28 μM for HCCLM3-LUC, 3.96 μM for HepG2, 2.44 μM for MCF-7 and 4.21 μM for MDA-MB-231), which was 2.94, 5.54, 12.56 and 7.72-fold stronger than that of ICA II. The preliminary SAR showed that the introduction of a alkyl amine substituent at 6-C was not favorable for the anticancer activity, while most of the 7-O-alkylamino derivatives exhibited good antitumor activity and the anticancer activity 7-O-alkylamino derivatives were influenced by the alkyl chain length and the different terminal amine substituents. Furthermore, the effects of compound 7g on apo...Continue Reading
References
Oct 8, 2003·Current Pharmaceutical Design·M GalanskiB K Keppler
Jun 6, 2006·Asian Journal of Andrology·Zhen-Bao Zhang, Qing-Tao Yang
Dec 23, 2009·Fitoterapia·Quan XiaShangquan Liu
Nov 30, 2010·Biomaterials·Yu GaoYaping Li
Sep 29, 2011·European Journal of Pharmacology·Liwen LiQinglong Guo
Nov 8, 2012·Bioorganic & Medicinal Chemistry·Nian-Guang LiJian-Ao Duan
Jan 26, 2013·Journal of Natural Products·Dharati JoshiArie Zask
Jun 5, 2013·Oncology Reports·Xian ZhangYinghua Li
Aug 26, 2014·In Vitro Cellular & Developmental Biology. Animal·Peng LiuZhengfeng Yin
Dec 18, 2014·International Journal of Molecular Sciences·Guang-Yi BaiZhong-Cheng Xin
Jan 7, 2015·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
Mar 21, 2015·Neuroscience·B LiuJ Dong
Jun 17, 2015·European Journal of Medicinal Chemistry·Chen WangXiao-Yi Wei
Jun 30, 2015·Cancer Letters·Ya-di GengLing-Yi Kong
Dec 4, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tao ChengYuan Zhao
Sep 20, 2016·Journal of Cellular and Molecular Medicine·Jianmei GaoQihai Gong
Jan 18, 2017·Combinatorial Chemistry & High Throughput Screening·Zhaokun YanJiumao Lin
Feb 6, 2017·Drug Delivery·Hongmei YanZhenhai Zhang
Mar 17, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Weijie XuJinhong Zheng
Apr 18, 2017·Experimental and Therapeutic Medicine·Hengrui LiuLi Yang
Apr 23, 2017·Bioorganic & Medicinal Chemistry Letters·Yunyun WangShifa Wang
Jun 18, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yuanyuan TangYun Liu