TY - JOUR
T1 - Design, synthesis and anticancer evaluation of novel Se-NSAID hybrid molecules
T2 - Identification of a Se-indomethacin analog as a potential therapeutic for breast cancer
AU - Ramos-Inza, Sandra
AU - Encío, Ignacio
AU - Raza, Asif
AU - Sharma, Arun K.
AU - Sanmartín, Carmen
AU - Plano, Daniel
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/12/15
Y1 - 2022/12/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ejmech.2022.114839
DO - 10.1016/j.ejmech.2022.114839
M3 - Article
C2 - 36257283
AN - SCOPUS:85139844740
SN - 0223-5234
VL - 244
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
M1 - 114839
ER -