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

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

  • Eur J Med Chem. 2022 Dec 15:244:114839. doi: 10.1016/j.ejmech.2022.114839.
Sandra Ramos-Inza 1,  Ignacio Encío 2,  Asif Raza 3,  Arun K Sharma 4,  Carmen Sanmartín 5,  Daniel Plano 6
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Technology and Chemistry, University of Navarra, Irunlarrea 1, E-31008, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008, Pamplona, Spain.
  • 2 Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008, Pamplona, Spain; Department of Health Sciences, Public University of Navarra, Avda. Barañain s/n, E-31008, Pamplona, Spain.
  • 3 Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State, USA.
  • 4 Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State, USA. Electronic address: asharma1@pennstatehealth.psu.edu.
  • 5 Department of Pharmaceutical Technology and Chemistry, University of Navarra, Irunlarrea 1, E-31008, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008, Pamplona, Spain. Electronic address: sanmartin@unav.es.
  • 6 Department of Pharmaceutical Technology and Chemistry, University of Navarra, Irunlarrea 1, E-31008, Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008, Pamplona, Spain. Electronic address: dplano@unav.es.
PMID: 36257283 DOI: 10.1016/j.ejmech.2022.114839
Abstract

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 IC50 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.

Keywords

Apoptosis; Cytotoxicity; NSAID; Selenium; Selenoester.

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