Design, synthesis and molecular docking study of novel quinoline–triazole molecular hybrids as anticancer agents

• A series of thirty-three quinoline-triazole molecular hybrids were synthesized. • In vitro antiproliferative activity of the new hybrids was evaluated using MTT assay. • 6 h, 8i, 8l and 8n were the most active compounds against MCF-7 cell line. • Drug-likeness and ADMET profiling revealed favourable properties. • DFT studies confirmed promising electronic characteristics. A series of novel thirty-three quinoline-triazole molecular hybrids were designed and synthesized via Copper catalyzed azide-alkyne cycloaddition (CuAAC) strategy. The in-vitro anticancer activity of the synthesized compounds was screened against human breast cancer MCF-7 cell line. Among these, compounds 6h, 8i, 8l and 8n have displayed superior anticancer activity (IC 50 values 0.39–3.65 μg/mL) than standard drug Doxorubicin (IC 50 value 3.69 μg/mL). Whereas, compounds 6b, 8d, 8f, 8h, 8m and 8o have displayed moderate anticancer activity with IC 50 values ranging from 5.52 to 11.49 μg/mL. Drug-likeness and ADMET profiling revealed favorable properties, and DFT studies confirmed promising electronic characteristics. Molecular docking indicated strong binding to CDK2 with affinities of -9.7 to -10 kcal/mol, supporting their potential as therapeutic candidates.