synthesis and antitumor activities of phenanthrene-based alkaloids合成和phenanthrene-based生物碱抗肿瘤活性.pdfVIP

Molecules 2009, 14, 5042-5053; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Antitumor Activities of Phenanthrene-Based Alkaloids Songtao Li 1,†, Li Han 1,†, Liang Sun 1, Dan Zheng 1, Jiang Liu 1, Yingbo Fu 1, Xueshi Huang 1,* and Zhanyou Wang 2,* 1 Department of Natural Products Chemistry, Pharmaceutical School, China Medical University, Shenyang 110001, China 2 Laboratory of Cell Engineering and Cell Therapy, College of Basic Medical Science, China Medical University, Shenyang 110001, China † These authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: xshuang@ (X.H.); zhanyouw@ (Z.W.). Received: 26 October 2009; in revised form: 25 November 2009 / Accepted: 2 December 2009 / Published: 7 December 2009 Abstract: A series of phenanthrene-based tylophorine derivatives (PBTs) were synthesized and their cytotoxic activities against the H460 human large-cell lung carcinoma cell line were evaluated. Among these compounds, N-(3-hydroxy-2,6,7-tri- methoxyphenanthr-9-ylmethyl)-L-prolinol (5a), and N-(3-hydroxy-2,6,7-trimethoxy- phenanthr-9-ylmethyl)-L-valinol (9) exhibited good activities, with IC50 values of 11.6 and 6.1 μM, respectively. Keywords: PBTs; synthesis; cytotoxicity 1. Introduction Phenanthroindolizidine alkaloids have been of considerable interest as anticancer agents because of their exceptionally potent antitumor activity [1]. Based