Novel Coumarin–Nucleobase Hybrids with Potential Anticancer Activity: Synthesis, In Vitro Cell-Based Evaluation, and Molecular Docking

TL;DR

Scientists created new compounds by combining coumarins and nucleobases, which showed promising anticancer activity in lab tests and computer modeling.

Contribution

The study introduces novel coumarin–nucleobase hybrids with anticancer potential, validated through synthesis, cell-based assays, and molecular docking.

Findings

Compound 9a showed strong anticancer activity with an IC50 of 24.19 ± 1.39 μM against colon carcinoma cells.

Molecular docking revealed high affinity of the compounds to the Topoisomerase 1–DNA complex.

In silico studies indicated low mutagenic and tumorigenic risk for the compounds.

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 9a 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. The in silico search for pharmacological targets was achieved through molecular docking studies on all active compounds, which suggested that the synthesized compounds possess a high affinity to the Topoisomerase 1–DNA complex, 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 molecular hybridization from natural derivative molecules is an interesting approach to seek new antitumor candidates.

Figures