# 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.

## Key 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.