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Synthesis and Biological Evaluations of Cytotoxic and Antiangiogenic Triterpenoids-Jacaranone Conjugates

[ Vol. 12 , Issue. 8 ]


Hua Sun, Partick Y.K. Yue, Shao-Rong Wang, Lihong Huo, Ying Zhao, Songbo Xie, Jens V. Kringelum, Ole Lund, Olivier Taboureau, Jun Zhou, Ricky N. S. Wong and Wei-Shuo Fang   Pages 775 - 785 ( 11 )


Background: The development of antiangiogenic agents arises as a more effective and selective therapeutic approach for the treatment of cancer. In addition to reduced acute toxicity, the efficacy of chemotherapy could be improved when administered in combination specific antiangiogenic with cytotoxic agents. The conjugation or hybridization of bifunctional molecules is one of the alternative rational design strategies for co-administration of anticancer drugs.

Objective and Methods: The goal of this work is to prepare the conjugates of an antiangiogenic triterpene, 3-oxo oleanolic acid, and structurally related triterpenoids with a cytotoxic semibenzoquinone, jacaranone. The cytotoxic, antiproliferative and antiangiogenic activities of segments and conjugates were determined. The possible targets of conjugates 6a-6h were predicted using Similarity Ensemble Approach (SEA).

Results: The results showed that these conjugates are more potent in both cytotoxic and antiangiogenic assays than their corresponding parent molecules, and are also selectively more active against melanoma cells B16 and metastatic B16BL6 than the two other cancer cell lines (A549 and MCF-7) tested. The predicted antiangiogenesis related targets could involve glycogen phosphorylase, neuraminidase, interferon gamma, and tubulin beta chain.

Conclusion: The bifunctional conjugates could be useful as dual acting antitumor/antigiogenic agents.


Antiangiogenesis, antitumor agent, conjugation, jacaranone, oleanolic acid.


State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No.1 Xian Nong Tan Street, Beijing, 100050, China.

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