Abstract 6356: Discovery of seleno allyl hybrid compounds, the Se incorporated mimics of naturally occurring garlic based allylic compounds, as potential anticancer agents

Abstract

Abstract Many synthetic derivatives of natural products have been found to exhibit biological activity towards cancer. One prominent example of such natural products are the garlic-based compounds. Given the well stablished preventive effects shown by garlic and some of its allylic components and a well-established chemopreventive and therapeutic effects shown by selenium (Se) compounds, we pursued to design Se-allyl hybrid compounds in order to increase efficacy as compared to naturally occurring allylic compounds. A total of 18 new selenoallyl (SeAl) compounds were designed following two different synthetic approaches. SeAl functionality was chosen to mimic the garlic bioactive allylic components. All the synthesized compounds were screened against colorectal (HT29 and HCT116) and mammary (MCF-7) cancer cell lines (48h treatment). Four most active compounds identified were submitted to the NCI Developmental Therapeutic Program (DTP). Two out of the four compounds were selected for the dose-response assay against a panel of 60 cancer cell lines. Both the compounds exhibited impressive cytotoxicity - lethal dose 50 (LD50) values below 9.2 µM in most of the melanoma and ovarian cancer cell lines tested (8 out of 9 for melanoma and 5 out of 7 for ovarian cancer cells for both compounds). Additionally, the Se-allyl derivative bearing an aspirin substituent presented a significant tumor size inhibition in a castration-resistant prostate cancer xenograft model at a dose of 4 mg/kg given intraperitoneally. Thus, this compound has the potential to be a promising candidate for prostate cancer treatment and potentially other cancers. To conclude, we firmly believe, based on the evidences obtained and presented herein, that structural modifications involving the hybridization approach with Se and naturally occurring allylic compounds could stand as a novel toolkit for anticancer drug development. Citation Format: Irene Talavera, Nora Astrain, Miguel Barajas, Ignacio Encío, Arun K. Sharma, Carmen Sanmartín, Daniel Plano. Discovery of seleno allyl hybrid compounds, the Se incorporated mimics of naturally occurring garlic based allylic compounds, as potential anticancer agents [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6356.