期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 244, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114839
关键词
Selenium; Selenoester; NSAID; Cytotoxicity; Apoptosis
资金
- Plan de Investigaci?on de la Universidad de Navarra, PIUNA
- Department of Pharmacology and Penn State Cancer Institute of the Penn State College of Medicine
- FPU program from the Spanish Ministry of Universities
- [EST19/00898]
- [FPU18/ 04679]
The study reported the cytotoxic effects of novel Se-NSAID analogs, showing that compounds 4a and 4d exhibit potential as chemotherapeutic drugs for breast cancer by inducing apoptosis and releasing the parent NSAID along with the Se fragment.
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 mu M 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.
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