Novel coumarin-nucleobase hybrids with potential anticancer activity: Synthesis, in-vitro cell-based evaluation, and molecular docking

23 May 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

A new series of compounds planned by molecular hybridization of the nucleobases uracil and thymine, or the xanthine theobromine, with coumarins, and linked through 1,2,3-triazole heterocycles were evaluated for their in vitro anticancer activity against the human tumor cell lines: colon carcinoma (HCT116), laryngeal tumor cells (Hep-2), and lung carcinoma cells (A549). The hybrid compound 7a exhibited better activity in the series, showing an IC50 of 24.19 ± 1.39 μM against the HCT116 cells, with a selectivity index (SI) of 6, when compared to the cytotoxicity against the non-tumor cell line HaCat. Molecular docking studies were performed on all active compounds and suggested that the synthesized compounds possess a high affinity to DNA Topoisomerase-1 protein, supporting their antitumor activity. The in silico toxicity prediction studies suggest that the compounds present a low risk of causing theoretical mutagenic and tumorigenic effects. These findings indicate that the molecular hybridization from natural derivative molecules is an interesting approach to seek new antitumor candidates.

Keywords

Molecular hybridization
coumarin
nucleobases
anticancer
molecular docking

Supplementary materials

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Supplementary Information
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Copies of 1H and 13C NMR of all new compounds
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