New 1,2,3-triazole linked flavonoid conjugates: Microwave-assisted synthesis, cytotoxic activity and molecular docking studies

The present study was carried out in an attempt to synthesize, under classical and microwave irradiation conditions, a new class of cytotoxic 1,2,3-triazole linked flavonols hybrids by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) to afford, in good yields (78-93%), 24 compounds 1'a-i, 2'a-h and 3'a-g, using three previously synthesized highly cytotoxic poly-halogenated flavonoids 1-3. The structures of the newly synthesized compounds were established by H-1 NMR, Jmod and ESI-HRMS. The prepared cycloadduct linked flavonols were evaluated for their cytotoxic activity against the human cell lines HCT-116 (Human colon carcinoma), MCF-7 (Human breast carcinoma) and OVCAR-3 (human ovarian carcinoma). The results showed that the cycloadducts 1'f, 1'g and 2'h against HCT-116 and 1'c, 2'g against OVCAR-3 were found to be the highest cytotoxic agents with IC50 values < 3.0 mu M, therefore, they may serve as a promising lead candidate for further investigation. The probable binding modes of the most active compounds were explored and further verified using molecular dynamics simulation. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

The study successfully synthesized a new class of cytotoxic compounds and evaluated their cytotoxic activity, identifying several compounds with potential for further investigation.