Antimicrobial and Cytotoxic Agents in 6-methyluracil Molecules of Amphiphilic Nature with Nonsaturated Substituents at Uracil Ring.

BACKGROUND

Infectious diseases caused by resistant microbes and oncological ailments pose a serious threat to human health. However, an effective and safe drug against them has not yet been found. Therefore, pyrimidine derivatives may be of interest as dual-acting drugs due to their potent antimicrobial and cytotoxic properties. The relevance of our research is confirmed by several recent patents dedicated to the antimicrobial and anticancer activity of pyrimidine-based molecules.

OBJECTIVE

The purpose of this study was to evaluate the antimicrobial and cytotoxic activity of some 6-methyluracil derivatives of an amphiphilic nature in vitro.

METHODS

Antimicrobial activity was studied by serial dilution. Cytotoxicity was tested using the MTT test. The mechanisms of antimicrobial and cytotoxic activity were analyzed using the methods of colorimetry, flow cytometry, and enzyme-linked immunosorbent assay.

RESULTS

The tested compounds have high antibacterial activity against resistant strains of Staphylococcus aureus and some bacteria from the group of ESKAPE pathogens. Outstanding results were obtained for the lead compounds in the human duodenal adenocarcinoma cell line (HuTu-80), for which cytotoxicity was shown at the level of 5-fluorouracil with a high selectivity index (SI = 8.0-10.0). The mechanism of antibacterial action is associated with the permeabilization of the bacterial membrane. The cytotoxic effect is due to the arrest of the cell cycle in the G1 phase and the induction of mitochondrial apoptosis. The introduction of the hexynyl group into the C5 position of the pyrimidine ring leads to increased antibacterial and cytotoxic activity.

CONCLUSION

The conducted studies allow us to consider the tested compounds as a promising basis for the creation of new effective antibacterial and сytotoxic agents.