Abstract 1631: Structural activity relationship studies of aza-podophyllotoxin derivatives on breast cancer cell line

Abstract

Abstract Podophyllotoxin is a natural precursor for the semi-synthesis of novel anticancer drugs and its an anti-tumor and antibacterial ligand derived from Podophyllum peltatum and Podophyllum emodi (Berberidaceae). Etoposide, etopophoside and tenoposide are anti-cancer drugs in pharmaceutical clinics since 1989 derived from a natural lignin podophyllotoxin. Synthesis of podophyllotoxin in a laboratory is one of the tedious and biggest challenges. In our previous work we developed a very simple method to synthesize extensively modified libraries of several novel derivatives, which were previously impossible to synthesize from podophyllotoxin (Kumar and Alegría, 2010). This method also allows us to explore the synthesis and applications of novel aza-podophyllotoxin derivatives which led to several new analogs with anti-cancer potential. Most of the compounds were found very active against Colon cancer, Melanoma, Ovarian, Renal, prostate and breast cancers at NCI upon a panel of 60 types of human cancer cell lines (Kumar, et.al. 2011). Based on structure activity relationship (SAR) of our compounds and their recent unpublished extraordinary activity especially against colon cancer (COLO 205) cell lines, we designed and synthesized novel aza-podophyllotoxin derivatives using microwave synthesis technique. We will be discussing the synthesis, SAR and biological activity of our novel 2,3-didehyropodophyllotoxin derivatives. Keywords: Pharmacology, Organic Chemistry and Toxicology Disclosure of Chemical Structure: The complete chemical structures of the compounds of the compounds used will be disclosed at the time of presentation at the meeting. Funded by INBRE-NIGMS-NIH gran #8 P20 GM 102475 and REU NSF 1262826 Citation Format: Michael Concepcion Santana, Ajay Kumar, Vineet Kumar, Antonio E. Alegria, Sanjay V. Malhotra. Structural activity relationship studies of aza-podophyllotoxin derivatives on breast cancer cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1631. doi:10.1158/1538-7445.AM2014-1631