Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules: Identification of a Se-indomethacin analog as a potential therapeutic for breast cancer.

A total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID analogs exhibited an increase in cytotoxic potency compared with parent NSAID scaffolds (aspirin, salicylic acid, naproxen, indomethacin and ketoprofen). Top five analogs were selected to further study their cytotoxicity in a larger panel of cancer cells and were also submitted to the DTP program of the NCI's panel of 60 cancer cell lines. Compounds 4a and 4d stood out with IC ₅₀ values below 10 μM in several cancer cells along with a selectivity index higher than 5 in breast cancer cells. Remarkably, analog 4d was found to inhibit cell growth notably in two breast cancer cell lines by inducing apoptosis, and to be metabolized to release the parent NSAID along with the Se fragment. Taken together, our results show that Se-NSAID analog 4d could be a potential chemotherapeutic drug for breast cancer.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Daniel Plano reports financial support was provided by Plan de Investigación de la Universidad de Navarra (PIUNA 2018-19). Arun K. Sharma reports financial support was provided by Department of Pharmacology and Penn State Cancer Institute of the Penn State College of Medicine.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)