Novel nitric oxide-releasing derivatives of pyranocarbazole as antitumor agents: Design, synthesis, biological evaluation, and nitric oxide release studies

Abstract

In this study, a series of novel furoxan-based nitric oxide (NO) releasing derivatives of pyranocarbazole alkaloids were designed, synthesized, and biologically evaluated against human cancer cell lines. The derivatives showed considerable antiproliferative activities (IC50 = 0.05-7.55 mu M) and most compounds showed higher activity in MDA-MB-231 than H460 and HeLa. Especially, the most active derivative 7a (IC50 = 0.05 mu M) against MDA-MB-231 was about 60 times stronger than lead compound, as well as equivalent to positive control taxol, and produced high levels of NO in MDA-MB-231. Furthermore, 7a could significantly inhibit the growth of MDA-MB-231 tumors in vivo with low toxicity and the PI3K/Akt signaling pathway. These results indicated that compound 7a could be a promising lead for further studies.