Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents

Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent beta-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin-murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z showed antitumor activities with half-maximal inhibitory concentration (IC50) values of 9.9 +/- 0.9, 8.6 +/- 1.4, 6.2 +/- 2.5, 9.9 +/- 0.5, and 5.7 +/- 1.2 mu M against the tested five cancer cell lines. Moreover, the effect of compound 8z on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 mu M, compound 8z showed a positive effect on angiogenesis. The results of this study contribute to the further elucidation of the biological regulatory role of heterobivalent beta-carbolines and provide helpful information on the development of vascular targeting antitumor drugs.