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