(1) Background: Infections by Candida species represent a serious threat to the health of immunocompromised individuals. Evidence has indicated that nerolidol has significant antifungal properties. Nonetheless, its use is restricted due to a low water solubility and high photosensitivity. The incorporation into liposomes may represent an efficient alternative to improve the physicochemical and biopharmaceutical properties of this compound. The present study aimed to characterize the antifungal properties of liposomal nerolidol, alone or in combination with fluconazole. Of note, this is the first study reporting the antifungal activity of liposomal nerolidol and its potentiating effect in association with fluconazole. (2) Methods: The Inhibitory Concentration 50%-IC₅₀ and minimum fungicide concentrations (MFC) of the substances against Candida albicans (CA), Candida tropicalis (CT), and Candida krusei (CK) were established by subculture in a solid medium. To evaluate the antifungal-enhancing effect, the MFC of fluconazole was determined in the presence or absence of subinhibitory concentrations of nerolidol (free or liposomal). The analysis of fungal dimorphism was performed through optical microscopy and the characterization of liposomes was carried out considering the vesicular size, polydispersion index, and zeta medium potential, in addition to a scanning electron microscopy analysis. (3) Results: The physicochemical characterization revealed that liposomes were obtained as homogenous populations of spherical vesicles. The data obtained in the present study indicate that nerolidol acts as an antifungal agent against Candida albicans and Candida tropicalis, in addition to potentiating (only in the liposomal form) the effect of fluconazole. However, the compound had little inhibitory effect on fungal dimorphism. (4) Conclusions: The incorporation of nerolidol into liposomes improved its antifungal-modulating properties.

The ability of dermatophytes to develop biofilms is possibly involved in therapeutic failure because biofilms impair drug effectiveness in the infected tissues. Research to find new drugs with antibiofilm activity against dermatophytes is crucial. In this way, riparins, a class of alkaloids that contain an amide group, are promising antifungal compounds. In this study, we evaluated the antifungal and antibiofilm activity of riparin III (RIP3) against Trichophyton rubrum, Microsporum canis, and Nannizzia gypsea strains. We used ciclopirox (CPX) as a positive control. The effects of RIP3 on fungal growth were evaluated by the microdilution technique. The quantification of the biofilm biomass in vitro was assessed by crystal violet, and the biofilm viability was assessed by quantifying the CFU number. The ex vivo model was performed on human nail fragments, which were evaluated by visualization under light microscopy and by quantifying the CFU number (viability). Finally, we evaluated whether RIP3 inhibits sulfite production in T. rubrum. RIP3 inhibited the growth of T. rubrum and M. canis from 128 mg/L and N. gypsea from 256 mg/L. The results showed that RIP3 is a fungicide. Regarding antibiofilm activity, RIP3 inhibited biofilm formation and viability in vitro and ex vivo. Moreover, RIP3 inhibited the secretion of sulfite significantly and was more potent than CPX. In conclusion, the results indicate that RIP3 is a promising antifungal agent against biofilms of dermatophytes and might inhibit sulfite secretion, one relevant virulence factor.

Cenostigma pluviosum var. peltophoroides, known as “sibipiruna,” is a plant rich in polyphenols used in traditional medicine for gastrointestinal disorders. The study aimed to investigate the chemical composition of the crude ethanolic extract of the stem bark (CEECP), evaluating its in vivo toxicity, genotoxicity, mutagenicity and anti-inflammatory activity. The plant material was macerated in 95% ethanol for 72 h, and the solvent was removed by rotary evaporation to obtain CEECP. Chemical characterization was performed by HPLC-ESI-MS/MS in negative mode. In vivo approaches were performed using male/female Swiss albino mice. Acute toxicity was assessed at a single high dose of 2000 mg/kg. Mutagenicity was investigated by the micronucleus test and genotoxicity by the comet assay, both at a dose of 2000 mg/kg. Anti-inflammatory activity was evaluated in carrageenan-induced paw edema and peritonitis models, at doses of 50, 100, and 200 mg/kg. HPLC-ESI-MS/MS analysis showed the presence of hydrolyzable tannins, phenolic acid heterosides, and biflavonoids. The safety profile of the CEECP was demonstrated for the first time, with no evidence of acute toxicity, mortality, mutagenicity, or genotoxicity at the tested doses. The extract significantly reduced paw edema in a dose-dependent manner at doses of 100 and 200 mg/kg, with inhibition rates of 65.78% and 73.12%, respectively, and also decreased leukocyte migration in the peritonitis model by 61.81% and 72.79% at the same doses. These findings indicate the CEECP as a source of pharmacologically relevant phytocompounds and, most notably, demonstrate its pronounced anti-inflammatory activity. Furthermore, the extract exhibited a favorable safety profile in the toxicological evaluations, highlighting the extract as a promising anti-inflammatory agent.

The Lauraceae family consists of approximately 70 genera and 2,500 species, with tropical and subtropical distribution. In Brazil, it comprises 400 species distributed in 25 genera. Among these, we highlight the genus Ocotea, with about 350 species. The present work had as objective to carry out the phytochemical study of Ocotea gardneri (MEISN) MEZ. For this, the botanical material was subjected to extraction, partition and chromatographic methods for isolation of the chemical constituents. The chemical structures of the compounds were determined by spectroscopic methods and comparisons with literature models. Chromatographic fractionation of the dichloromethane phase of Ocotea gardneri resulted in the isolation of triterpene 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexene (squalene), 3,4,5-trimethoxybenzaldehyde and the glycosylated steroid sitosterol-3-O-β-D-glucopyranoside. From the ethyl acetate phase was isolated the flavone 3, 5, 7, 3',4'-pentahydroxyflavone (quercetin) and two flavonols (-) 2- (3,4-dihydroxyphenyl) -4H-chromene-3,5,7-triol (epicatechin) and (+) 2- (3,4-dihydroxyphenyl) -4H-chromene-3,5,7-triol (catechin). All compounds are being reported for the first time in the species. Ocotea gardneri has been shown to be a promising species due to the variety of isolated chemical compounds.