title: Synthesis, anti-tumor and anti-angiogenic activity evaluations of asiatic Acid amino Acid derivatives.
abstract: Fifteen semi-synthetic derivatives of asiatic acid (AA) have been synthesized and evaluated for their biological activities. The successful modification of these compounds at the C-2, C-3, C-23 and C-28 positions was confirmed using NMR, MS and IR spectra. Further, their anti-tumor effects were evaluated in vitro using different cancer cell lines (HeLa, HepG2, B16F10, SGC7901, A549, MCF7 and PC3), while their anti-angiogenic activities were evaluated in vivo using a larval zebrafish model. Among the derivatives, compounds 4-10 showed more potent cytotoxic and anti-angiogenic effects than AA, while compounds 11-17 had significantly less effects. The new derivative 10 was also included in finished formulations to evaluate its stability using HPLC due to its potential topical use. The derivative 10 had markedly better anti-tumor activities than both AA and other derivatives, with similar stability as its parent compound AA.
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing 210023, China. jingyueshadow@126.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing 210023, China. jiyehanyan@126.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing 210023, China. emilygy0131@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing 210023, China. xmj1011@163.com.
authors.forename: Minjie
authors.initials: M
authors.lastname: Xu
authors.affiliation: Center for New Drug Research and Development, College of Life Science, Nanjing Normal University, Nanjing 210023, China. gongzhunan@njnu.edu.cn.
authors.forename: Zhunan
authors.initials: Z
authors.lastname: Gong
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects* / Q000196:embryology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D053978:Pentacyclic Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; C017032:asiatic acid