Abstract 5450: New se-nsaid hybrid molecules as potent and selective cytotoxic agents against breast cancer cells

Abstract

Abstract Breast cancer is currently the most frequently diagnosed cancer and one of the leading causes of mortality among women worldwide. The introduction of a selenium atom (Se) in the structure of organic molecules has been demonstrated to be a valid approach in the design of novel chemotherapeutic agents with several biological effects, including antitumoral activity. In addition, several epidemiological, preclinical, and clinical studies support the chemopreventive and chemotherapeutic potential use of non-steroidal anti-inflammatory drugs (NSAIDs).On the basis of these findings, and taking into account the results of previous studies by our research group, we have developed a new series of twenty-five NSAID analogs bearing Se in the form of selenoesters modulated with different functional groups. The new compounds were tested in four cancer cell lines (HTB-54, DU-145, HT-29 and MCF-7) and two non-malignant cells (184B5 and BEAS-2B). The cytotoxicity of the five most potent and selective molecules was further studied in other cancer cell lines as well. Compounds 4a and 4d stood out as the most selective compounds with a selectivity index at least 5-fold higher in breast cancer cells. Compound 4d showed IC50 values below 10 µM and was found to be more potent than 4a in almost every cell line tested. Additionally, 4d effectively induced apoptosis in triple negative (MDA-MB-231) and estrogen receptor-positive (MCF-7) breast cancer cell lines. Taken together, this study supports the design of new derivatives containing Se as potential anticancer agents. Citation Format: Sandra Ramos-Inza, Ignacio Encío, Asif Raza, Arun Sharma, Carmen Sanmartín, Daniel Plano. New se-nsaid hybrid molecules as potent and selective cytotoxic agents against breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5450.