synthesis and biological activity of 23-hydroxybetulinic acid c-28 ester derivatives as antitumor agent candidates合成和生物活性c-28 23-hydroxybetulinic酸酯衍生物的抗肿瘤剂的候选人.pdfVIP

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synthesis and biological activity of 23-hydroxybetulinic acid c-28 ester derivatives as antitumor agent candidates合成和生物活性c-28 23-hydroxybetulinic酸酯衍生物的抗肿瘤剂的候选人.pdf

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synthesis and biological activity of 23-hydroxybetulinic acid c-28 ester derivatives as antitumor agent candidates合成和生物活性c-28 23-hydroxybetulinic酸酯衍生物的抗肿瘤剂的候选人

Molecules 2012, 17, 8832-8841; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Biological Activity of 23-Hydroxybetulinic Acid C-28 Ester Derivatives as Antitumor Agent Candidates Yi Bi 1, Jinyi Xu 2,3,*, Fei Sun 2, Xiaoming Wu 3,*, Wencai Ye 4, Yijun Sun 5 and Wenwen Huang 1 1 School of Pharmacy, Yantai University, Yantai 264005, Shandong, China 2 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, Jiangsu, China 3 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, Jiangsu, China 4 Department of Phytochemistry, China Pharmaceutical University, Nanjing 210009, Jiangsu, China 5 Drug Screening Center, Nanjing KeyGen Biotech. Co. Ltd., Nanjing 210012, Jiangsu, China * Authors to whom correspondence should be addressed; E-Mails: jinyixu@ (J.X.); xmwu@ (X.W.); Tel.: +86-258-327- 1445 (J.X.); Fax: +86-258-330-2827 (X.W.). Received: 29 May 2012; in revised form: 17 July 2012 / Accepted: 18 July 2012 / Published: 25 July 2012 Abstract: 23-Hydroxybetulinic acid (1) served as the precursor for the synthesis of C-28 ester derivatives. The target compounds were evaluated in vitro for their antitumor activities against five cell lines (A549, BEL-7402, SF-763, B16 and HL-60). Among the obtained compounds, 6i had the most potent antitumor activity, with the IC50 values of 8.35 µM in HL-60 cells and showed similar antitumor activity as cyclophosphamide in