Abstract 3830: Synthesis and anticancer activity of novel prodigiosin analogs

Abstract

Abstract We recently reported that Prodigiosin is a potent p53 pathway restoring small molecule that acts through p73 and by interfering with p73:mutant p53 protein interaction (Hong et al., Cancer Research, 2014). Prodigiosin is the parent member of the tripyrrole alkaloid family of natural products that shows potent anti-cancer activity against tumors with mutated p53. To improve pharmacological and medicinal properties of Prodigiosin including p73 induction and restoration of the p53 pathway in tumors with mutated p53, two new series of analogs were synthesized. We introduced carboxylic group substituents either directly on the C-ring or on the side-chain of the C-ring. Carboxylic group allowed for further derivatization of Prodigiosin. A number of new analogs have been prepared and tested for their anticancer activity. Preliminary biological activity assay showed that new compounds inhibited cancer cell proliferation from 0.1 μM to 10 μM both in p53 mutated SW480 and wild-type HCT116 colorectal cancer cell lines. Some of the newly synthesized compounds can induce p53 transcriptional reporter activity in p53 mutated SW480 colorectal cancer cells. Our ongoing experiments are focused on the signaling mechanism of apoptosis induced by the new analogs, identification of molecular targets of the compounds, and in vivo studies of Prodigiosin analogues as single agents or in combination with chemotherapy or targeted therapy. Citation Format: Xiaobing Tian, Shengliang Zhang, Wafik S. El-Deiry. Synthesis and anticancer activity of novel prodigiosin analogs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3830.