"ATIVIDADE MULTIFUNCIONAL DO PEPTÍDEO RQ18: PROPRIEDADES ANTIBACTERIANA, ANTIFÚNGICA E ANTICANCERÍGENA"

Abstract

The spread of bacterial and fungal infections resistant to conventional antimicrobials and the increasing number of cancer cases are the most threatening public health problems worldwide. The impact of treating these diseases and maintaining health represents a high cost, not only economically but also socially. Antimicrobial peptides (AMPs) have been considered promising candidates for controlling these diseases. This work aimed to evaluate the antibacterial, antifungal, antibiofilm, and anticancer activity, as well as the mechanism of action of the AMP RQ18 against clinically relevant cells for humans and animals. The characterization of RQ18 activity was previously analyzed through computational tools. After chemical synthesis, the minimum inhibitory concentrations (MIC), minimum bactericidal and fungicidal concentrations (MBC and MFC), antibiofilm activity, time-dependent death kinetics, anticancer activity, and mechanism of action of the peptide RQ18 on target cells and through molecular dynamics were determined. Toxicity assays were evaluated in vitro and in vivo. The cationic peptide RQ18 inhibited the growth of bacteria and fungi from 1.25 μM (MIC) and was able to kill cells from clinical isolates of Staphylococcus aureus in 1 hour and Candida tropicalis in 2 hours. Furthermore, RQ18 showed synergistic effect with conventional antimicrobials. RQ18 was also determined as an antibiofilm agent, reducing biofilm formation and promoting eradication of mature biofilms of C. tropicalis. The mechanism of action of RQ18 involves damage to the plasma membrane, confirmed by fluorescence microscopy with SytoxTM green and molecular dynamics. The high selectivity of the peptide for cancer cell membranes was demonstrated by its low IC50 value at 4.4 µM and causing apoptosis to B16F10- Nex2 cells. On the other hand, the peptide showed no toxic effect on RAW 264.7 cells (up to 64 µM) and G. mellonella larvae, up to 100 µM, demonstrating high cellular selectivity for infectious cells. Therefore, the peptide RQ18 represents a promising strategy in controlling antimicrobial-resistant infections, being a membrane-active with triple antibacterial, antifungal, and anticancer activity, without compromising the viability of mammalian cells.