Selective Induction of DNA Damage and Cell Cycle Arrest Mediated by Chromone-Triazole Dyads Derivatives: Effects on Breast and Prostate Cancer Cells.

Autor: Saher L; Department of Medical Sciences, Institute of Biomedicine, University of Aveiro, 3810-183, Aveiro, Portugal.; Department of Chemistry LAQV-REQUIMTE, University of Aveiro, 3810-183, Aveiro, Portugal.; Center de Recherche Scientifique et Technique en Analyses Physico-Chimiques CRAPC, BP384, Bou-Ismail, 42004, Algeria., Monteiro FL; Department of Medical Sciences, Institute of Biomedicine, University of Aveiro, 3810-183, Aveiro, Portugal., Rocha DHA; Department of Chemistry CICECO, Institute of Material, University of Aveiro, 3810-183, Aveiro, Portugal., Albuquerque HMT; Department of Chemistry LAQV-REQUIMTE, University of Aveiro, 3810-183, Aveiro, Portugal., Silva AMS; Department of Chemistry LAQV-REQUIMTE, University of Aveiro, 3810-183, Aveiro, Portugal., Helguero LA; Department of Medical Sciences, Institute of Biomedicine, University of Aveiro, 3810-183, Aveiro, Portugal.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2023 Jul; Vol. 20 (7), pp. e202300251. Date of Electronic Publication: 2023 Jun 30.
DOI: 10.1002/cbdv.202300251
Abstrakt: Chromones and triazoles are groups of heterocyclic compounds widely known to exhibit a broad spectrum of biological activities. The combination of these two pharmacophores could result in multiple mechanisms of action to increase the potency of anticancer drugs and reduce their side effects. The in vitro antitumor effect of eight chromone-based compounds was evaluated in breast (T-47D and MDA-MB-231) and prostate (PC3) cancer cell lines, and in non-cancerous human mammary epithelial cells (HuMEC) using a resazurin-based method. Flow cytometry was used to evaluate the cell cycle and cell death, and ɣ-H2AX detection to identify DNA damage. The compounds showed selective cytotoxicity against cancer cell lines, with (E)-2-(2-(5-(4-methoxyphenyl)-2H-1,2,3-triazol-4-yl)vinyl)-4H-chromen-4-one (compound 2 a) being more potent in non-metastatic T-47D cells (IC 50 0.65 μM). Replacing the hydrogen by a methyl group on the triazole ring in compound 2 b enhanced the cytotoxic activity up to IC 50 0.24 μM in PC3, 0.32 μM in MDA-MB-231 and 0.52 μM in T-47D. Compound 2 b was 3-fold more potent than doxorubicin in PC3 (IC 50 0.73 μM) and 4-fold in MDA-MB-231 (IC 50 1.51 μM). The addition of tetrahydroisoindole-1,3-dione moiety in compound 5 did not improve its effectiveness in any of the cell lines but it exerted the lowest cytotoxic effect in HuMEC (IC 50 221.35 μM). The compounds revealed different cytotoxic mechanisms: 2 a and 2 b induced G2/M arrest, and compound 5 did not affect the cell cycle.
(© 2023 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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