synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents合成和生物评价新川芎嗪衍生物作为抗肿瘤剂.pdfVIP

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synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents合成和生物评价新川芎嗪衍生物作为抗肿瘤剂.pdf

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synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents合成和生物评价新川芎嗪衍生物作为抗肿瘤剂

Molecules 2012, 17, 4972-4985; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Biological Evaluation of New Ligustrazine Derivatives as Anti-Tumor Agents 1 1 2 1 1 1 Penglong Wang , Gaimei She , Yanan Yang , Qiang Li , Honggui Zhang , Jie Liu , Yinqiu Cao 1, Xin Xu 1 and Haimin Lei 1,* 1 School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China 2 Institute of Materia Medica, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100050, China * Author to whom correspondence should be addressed; E-Mail: hm_lei@; Tel.: +86-010-8473-8641. Received: 19 March 2012; in revised form: 18 April 2012 / Accepted: 20 April 2012 / Published: 30 April 2012 Abstract: To discover new anti-cancer agents with multi-effect and low toxicity, a series of ligustrazine derivatives were synthesized using several effective anti-tumor ingredients of Shiquandabu Wan as starting materials. Our idea was enlightened by the “combination principle” in drug discovery. The ligustrazine derivatives’ anti-tumor activities were evaluated on the HCT-8, Bel-7402, BGC-823, A-549 and A2780 human cancer cell lines. In addition the angiogenesis activities were valued by the chick chorioallantoic membrane (CAM) assay. 1,7-bis(4-(3,5,6-Trimethylpyrazin-2-yl)-3-methoxyphenyl)-1,6-heptadiene- 3,5-dione (4) and 3α,12α-dihydroxy