Design, synthesis, characterization, in silico studies, and in vitro anticancer evaluation of novel 7-methoxyquinolone-substituted triazole hybrids

新型7-甲氧基喹诺酮取代三唑杂合物的设计、合成、表征、计算机模拟研究和体外抗癌评价

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Abstract

AIMS: The quinolone scaffold is a crucial member of the heterocyclic compound family in modern medicinal chemistry, exhibiting a broad range of biological activities. Since 4-quinolones are known to interact with significant drug targets, and due to the remarkable pharmacological properties of 1,2,3-triazole compounds, a molecular hybridization approach was used to design novel 7-methoxyquinolone-substituted triazole hybrid conjugates (QN1-QN11). MATERIALS AND METHODS: These hybrid compounds were evaluated to determine their anticancer activities in various breast and colon cancer cell lines, including BT20, MDA-MB-231, MCF7, and HT29. In addition, the apoptotic-like morphological changes in aggressive MDA-MB-231 cells were observed following treatment with the compounds for 48 hours. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and MM/GBSA calculations, were carried out for the synthesized compounds against important cancer drug targets. RESULTS: The highly cytotoxic agents QN10 and QN7 were identified with IC(50) values of 4.49 ± 0.68 µM and 19.05 ± 1.58 µM in BT20 and HT29 cell lines, respectively. In addition, the morphologically changes were observed on MDA-MB-231 cells. CONCLUSIONS: These findings show that the synthesized click products are highly cytotoxic agents in cancer cell lines and may be considered as potential candidates for enzyme inhibition.

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