Staphylococcus aureus is able to rapidly develop mechanisms of resistance to various drugs and to form strong biofilms, which makes it necessary to develop new antibacterial drugs. The essential oil of Melaleuca alternifolia is used as an antibacterial, a property believed to be mainly due to the presence of terpinen-4-ol. Based on this, the objective of this study was to evaluate the antibacterial and antibiofilm potential of terpinen-4-ol against S. aureus. The Minimal Inhibitory and Minimal Bactericidal Concentrations (MIC and MBC) of terpinen-4-ol were determined, and the effect of its combination with antibacterial drugs as well as its activity against S. aureus biofilms were evaluated. In addition, an in silico analysis of its pharmacokinetic parameters and a molecular docking analysis were performed. Terpinen-4-ol presented a MIC of 0.25% (v/v) and an MBC of 0.5% (v/v) (bactericidal action); its association with antibacterials was also effective. Terpinen-4-ol has good antibiofilm activity, and the in silico results indicated adequate absorption and distribution of the molecule in vivo. Molecular docking indicated that penicillin-binding protein 2a is a possible target of terpinen-4-ol in S. aureus. This work highlights the good potential of terpinen-4-ol as an antibacterial product and provides support for future pharmacological studies of this molecule, aiming at its therapeutic application.

The genus Candida is one of the main causes of otomycosis. The growing index of fungal strains resistant to antifungals makes necessary the search for new agents and α-pinene is a phytoconstituent present in plants with remarkable antimicrobial activity, which becomes an interesting object of study. Thus, the objective of this research was to evaluate the antifungal activity of α-pinene against Candida species isolated from otomycosis, determining the Minimum Inhibitory and Fungicide Concentrations, micromorphological analysis and verifying the effects of the association with boric acid. α-pinene showed significant antifungal activity, with greater inhibitory activity against C. parapsilosis, fungicidal action and proved to be effective in inhibiting fungal structures, such as pseudo-hyphae and promoting a marked decrease in blastoconidia. The combination of α-pinene with boric acid produced additive effects that may be interesting for use in clinical practice. Graphical Abstract

The increase in Staphylococcus aureus resistance to conventional antibacterials and persistent infections related to biofilms, as well as the low availability of new antibacterial drugs, has made the development of new therapeutic alternatives necessary. Medicinal plants are one of the main sources of bioactive molecules and myrtenol is a natural product with several biological activities, although its antimicrobial activity is little explored. Based on this, the objective of this study was to evaluate the antibacterial activity of myrtenol against S. aureus, determining the minimum inhibitory and bactericidal concentrations (MIC and MBC), investigating the possible molecular target through the analysis of molecular docking. It also aimed to evaluate the effect of its combination with antibacterial drugs and its activity against S. aureus biofilms, in addition to performing an in silico analysis of its pharmacokinetic parameters. Myrtenol showed MIC and MBC of 128 µg/mL (bactericidal action) and probably acts by interfering with the synthesis of the bacterial cell wall. The effects of the association with antibacterials demonstrate favorable results. Myrtenol has remarkable antibiofilm activity and in silico results indicate a good pharmacokinetic profile, which make myrtenol a potential drug candidate for the treatment of infections caused by S. aureus.

The enantiomers (R)-(+)-β-citronellol and (S)-(−)-β-citronellol are present in many medicinal plants, but little is understood about their bioactivity against Candida yeasts. This study aimed to evaluate the behavior of positive and negative enantiomers of β-citronellol on strains of Candida albicans and C. tropicalis involved in candidemia. The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined. The evaluation of growth kinetics, mechanism of action, and association studies with Amphotericin B (AB) using the checkerboard method was also performed. R-(+)-β-citronellol and S-(−)-β-citronellol presented a MIC_50% of 64 µg/mL and a MFC_50% of 256 µg/mL for C. albicans strains. For C. tropicalis, the isomers exhibited a MIC_50% of 256 µg/mL and a MFC_50% of 1024 µg/mL. In the mechanism of action assay, both substances displayed an effect on the fungal membrane but not on the fungal cell wall. Synergism and indifference were observed in the association of R-(+)-β-citronellol and AB, while the association between S-(−)-β-citronellol and AB displayed synergism, additivity, and indifference. In conclusion, both isomers of β-citronellol presented a similar profile of antifungal activity. Hence, they can be contemplated in the development of new antifungal drugs providing that further research is conducted about their pharmacology and toxicity.

In the current context of emerging drug-resistant fungal pathogens such as Candida albicans and Candida parapsilosis, discovery of new antifungal agents is an urgent matter. This research aimed to evaluate the antifungal potential of 2-chloro-N-phenylacetamide against fluconazole-resistant clinical strains of C. albicans and C. parapsilosis. The antifungal activity of 2-chloro-N-phenylacetamide was evaluated in vitro by the determination of the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), inhibition of biofilm formation and its rupture, sorbitol and ergosterol assays, and association between this molecule and common antifungal drugs, amphotericin B and fluconazole. The test product inhibited all strains of C. albicans and C. parapsilosis, with a MIC ranging from 128 to 256 µg.mL^-1, and a MFC of 512-1,024 µg.mL^-1. It also inhibited up to 92% of biofilm formation and rupture of up to 87% of preformed biofilm. 2-chloro-N-phenylacetamide did not promote antifungal activity through binding to cellular membrane ergosterol nor it damages the fungal cell wall. Antagonism was observed when combining this substance with amphotericin B and fluconazole. The substance exhibited significant antifungal activity by inhibiting both planktonic cells and biofilm of fluconazole-resistant strains. Its combination with other antifungals should be avoided and its mechanism of action remains to be established.

Klebsiella pneumoniae causes a wide range of community and nosocomial infections. The high capacity of this pathogen to acquire resistance drugs makes it necessary to develop therapeutic alternatives, discovering new antibacterial molecules. Acetamides are molecules that have several biological activities. However, there are no reports on the activity of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide. Based on this, this study aimed to investigate the in vitro antibacterial activity of this molecule on K. pneumoniae, evaluating whether the presence of the chloro atom improves this effect. Then, analyzing its antibacterial action more thoroughly, as well as its cytotoxic and pharmacokinetic profile, in order to contribute to future studies for the viability of a new antibacterial drug. It was shown that the substance has good potential against K. pneumoniae and the chloro atom is responsible for improving this activity, stabilizing the molecule in the target enzyme at the site. The substance possibly acts on penicillin-binding protein, promoting cell lysis. The analysis of cytotoxicity and mutagenicity shows favorable results for future in vivo toxicological tests to be carried out, with the aim of investigating the potential of this molecule. In addition, the substance showed an excellent pharmacokinetic profile, indicating good parameters for oral use.