Eldehnaa, W M, Taghourb, M S, Al-Warhi, T, Nocentini, A, Elbadawi, M M, Mahdy, H A, Abdelrahman, M A, Alotaibi, O J, Aljaeed, N, Elimam, D M, Afarinkia, K ORCID: https://orcid.org/0000-0003-2819-4364, Abdel-Aziz, H A and Supuran, C T (2022) Discovery of 2,4-thiazolidinedione-tethered coumarins as novel selective inhibitors for carbonic anhydrase IX and XII isoforms. JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 37 (1). pp. 531-541.

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Abstract

Different 2,4-thiazolidinedione-tethered coumarins 5a–b, 10a–n and 11a–d were synthesised and evaluated for their inhibitory action against the cancer-associated hCAs IX and XII, as well as the physiologically dominant hCAs I and II to explore their selectivity. Un-substituted phenyl-bearing coumarins 10a, 10 h, and 2-thienyl/furyl-bearing coumarins 11a–c exhibited the best hCA IX (KIs between 0.48 and 0.93 mM) and hCA XII (KIs between 0.44 and 1.1 mM) inhibitory actions. Interestingly, none of the coumarins had any inhibitory effect on the off-target hCA I and II isoforms. The sub-micromolar compounds from the biochemical assay, coumarins 10a, 10 h and 11a–c, were assessed in an in vitro antiproliferative assay, and then the most potent antiproliferative agent 11a was tested to explore its impact on the cell cycle phases and apoptosis in MCF-7 breast cancer cells to provide more insights into the anticancer activity of these compounds.

Item Type:	Article
Identifier:	10.1080/14756366.2021.2024528
Subjects:	Medicine and health > Clinical medicine > Therapeutics
Depositing User:	Kamyar Afarinkia
Date Deposited:	04 Nov 2024 09:35
Last Modified:	04 Nov 2024 10:34
URI:	https://repository.uwl.ac.uk/id/eprint/12826

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