ArticleMedicinal chemistry (Shariqah (United Arab Emirates))2025
Design and Development of [1,2,4]Triazolo[4,3-b][1,2,4]triazines as Potential Anticancer Agents with Genotoxicity and Apoptotic Activity.
Article in Medicinal chemistry (Shariqah (United Arab Emirates)), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
aimsIn this current study, a new series of triazolo-triazine derivatives were designed and synthesized as potential anticancer agents.
methodsThe antiproliferative activity of the new compounds was evaluated against four different cancerous cell lines (MDA-MB-231, HCT-116, A549, and HT-29) using an MTT assay. To evaluate the mechanism of action, the ability of the best compound in apoptosis induction and DNA damage was evaluated using the flow cytometry technique and comet assays. Furthermore, molecular docking simulation was used to investigate their interactions with the two targets, VEGFR2 and c-Met kinases.
resultsResults showed that 6-(4-bromophenyl)-3-((4-methoxybenzyl)thio)-[1,2,4]triazolo[4,3- b][1,2,4]triazine (8c) demonstrated the best anti-proliferative activity against the human colorectal carcinoma cells HCT-116 with an IC
conclusionOur results showed that compound 8c significantly increased cell death through apoptosis induction and caused a significant increase in genotoxicity. Furthermore, it was found that the tested compound 8c, with a selectivity index of 1.74, possessed selective antiproliferative activity towards the colorectal cancer cell line HCT-116 compared to the normal fibroblast cell line. These findings could be useful in the development of novel VEGFR2/c-Met dual-targeted inhibitors in the future.
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