20.500.12556/DKUM-89965 Novel coumarin-6-sulfonamide-chalcone hybrids as glutathione transferase P1-1 inhibitors Multidrug resistance (MDR) mechanisms in cancer cells are greatly influenced by glutathione transferase P1-1 (hGSTP1-1). The use of synthetic or natural compounds as hGSTP1-1 inhibitors is considered an effective approach to overcome MDR. Nine compounds consisting of coumarin-6-sulfonamide linked to chalcone derivatives were synthesized and evaluated for their ability to inhibit hGSTP1-1. Among the synthetic derivatives, compounds 5g, 5f, and 5a displayed the most potent inhibitory effect, with IC50 values of 12.2 ± 0.5 μΜ, 12.7 ± 0.7 and 16.3 ± 0.6, respectively. Kinetic inhibition analysis of the most potent molecule, 5g, showed that it behaves as a mixed-type inhibitor of the target enzyme. An in vitro cytotoxicity assessment of 5a, 5f, and 5g against the human prostate cancer cell lines DU-145 and PC3, as well as the breast cancer cell line MCF-7, demonstrated that compound 5g exhibited the most pronounced cytotoxic effect on all tested cell lines. Molecular docking studies were performed to predict the structural and molecular determinants of 5g, 5f, and 5a binding to hGSTP1-1. In agreement with the experimental data, the results revealed that 5g exhibited the lowest docking score among the three studied inhibitors as a consequence of shape complementarity, governed by van der Waals, hydrogen bonds and a π-π stacking interaction. These findings suggest that coumarin-chalcone hybrids offer new perspectives for the development of safe and efficient natural product-based sensitizers that can target hGSTP1-1 for anticancer purposes. cancer cells glutathione transferase P1-1 hGSTP1-1 coumarin-6-sulfonamide chalcone derivatives rakave celice kalkon derivativi true false true Public Library of Science (PLoS), United States Angleški jezik Slovenski jezik https://journals.plos.org/plosone/ © 2024 Sabt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Članek v reviji 2024-08-20 09:48:18 2024-08-20 09:48:19 2026-01-31 03:16:01 0000-00-00 00:00:00 2024 0 0 17 str. Published: August 14, 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 2024-03-06 2024-06-10 2024-08-14 543.645.4 204635395 10.1371/journal.pone.0306124 1932-6203 journal.pone.0306124.pdf journal.pone.0306124.pdf 1 2E071A9ACD21A5348416EB4BFB10ABCA 3e38125c304e979b0e1ef7b2b47e4e71520d0743cb28527ff774a17872be04b8 56dbb08b-fdd0-11f0-8805-00155d00018d https://dk.um.si/Dokument.php?lang=slv&id=202863 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0306124#sec021 0 5e2f6ca9-fdd0-11f0-8805-00155d00018d https://dk.um.si/Dokument.php?lang=slv&id=202864 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0