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Candida spp. is an opportunistic pathogen capable of causing superficial to invasive infections. Morphological transition is one of the main virulence factors of this genus and, therefore, is an important variable to be considered in pharmacological interventions. Riparins I, II, III, and IV are alkamide‐type alkaloids extracted from the unripe fruit of Aniba riparia, whose remarkable pharmacological properties were previously demonstrated. This work aimed to evaluate in silico and in vitro the inhibitory effects of Riparins on the morphological transition of Candida albicans, Candida tropicalis, and Candida krusei. Molecular docking was applied to analyze the inhibitory effects of riparins against proteins such as N‐acetylglucosamine, CYP‐51, and protein kinase A (PKA) using the Ramachandran plot. The ligands were prepared by MarvinSketch and Spartan software version 14.0, and MolDock Score and Rerank Score were used to analyze the affinity of the compounds. In vitro analyses were performed by culturing the strains in humid chambers in the presence of riparins or fluconazole (FCZ). The morphology was observed through optical microscopy, and the size of the hyphae was determined using the ToupView software. In silico analysis demonstrated that all riparins are likely to interact with the molecular targets: GlcNAc (>50%), PKA (>60%), and CYP‐51 (>70%). Accordingly, in vitro analysis showed that these compounds significantly inhibited the morphological transition of all Candida strains. In conclusion, this study demonstrated that riparins inhibit Candida morphological transition and, therefore, can be used to overcome the pathogenicity of this genus. [ABSTRACT FROM AUTHOR]

Fungi of the Candida genus are responsible for invasive candidiasis, which affects people all over the world and has high mortality rates. This is due to their virulence factors, which give them great resistance and pathogenicity. In addition, the emergence of multidrug-resistant strains makes it difficult to treat these infections. In this way, natural products have emerged as an alternative to standard drugs, where plants known for their medicinal properties such as Turnera subulata become attractive to research. The present work aimed to analyze the ethanol extract of Turnera subulata leaves against standard strains of Candida albicans, Candida krusei and Candida tropicalis using broth microdilution techniques. The identification of the compounds in T. subulata leaves by LC-MS revealed the presence of a wide variety of substances such as carboxylic acids and terpenes, with flavonoids and fatty acids being more evident. The antifungal assays showed that the extract was not able to inhibit the growth of the tested strains at concentrations with a clinical relevance. However, at higher concentrations, it was able to inhibit the fungal dimorphism of C. albicans and C. tropicalis. It is possible that the T. subulata extract has potential as an inhibitor of fungal virulence factors without affecting the cell viability. Further research should be carried out in order to assess its inhibitory potential for other fungal virulence factors. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

The emergence of fungal resistance to commercial drugs has been a major problem for the WHO. In this context, research with natural products is promising in the discovery of new active substances. Thus, this work evaluated the antifungal effect of a medicinal plant (i.e., Mesosphaerum suaveolens) against strains of the genus Candida, tested the combined effect with the drug fluconazole, and, finally, determined the phenolic constituents present in the species. Initially, aqueous extracts of leaves (AELMs) and aerial parts (AEAPMs) of the species were prepared. For microbiological assays, the minimum fungicidal concentration was determined by broth microdilution, and the combined effect of fluconazole extracts were verified by sub-inhibitory microdilution concentrations (CFM/8) followed by spectrophotometric readings which were used to determine the IC50. HPLC detected the presence of flavonoids and phenolic acids, detecting eight compounds present in the samples of which caffeic acid and quercetin were major components. The AELMs modulated fluconazole activity since it decreased fluconazole's IC50 from 7.8 µg/mL to an IC50 of 4.7 µg/mL (CA LM 77) and from 28.8 µg/mL to 18.26 µg/mL (CA INCQS 40006) for the C. albicans strains. The AEAPMs were able to potentiate the effect of fluconazole more effectively than the AELMs. Such an effect was significant for the 16 µg/mL concentration for CA LM 77 and 32 µg/mL for CA INCQS 40006. The AEAPMs as well as the AELMs presented clinically relevant activities for C. tropicalis strains. For the C. tropicalis LM 23 strain, the AEPMs obtained an IC50 of 25 µg/mL and the AELMs an IC50 of 359.9 µg/mL. [ABSTRACT FROM AUTHOR]

The development of fungal resistance to antifungal drugs has been worsening over the years and as a result research on new antifungal agents derived from plants has intensified. Eugenia uniflora L. (pitanga) has been studied for its various biological actions. In this study the chemical composition and antifungal effects of the E. uniflora essential oil (EULEO) were investigated against Candida albicans (CA), Candida krusei (CK) and Candida tropicalis (CT) standard strains. The essential oil obtained through hydro-distillation was analyzed by gas chromatography coupled to mass spectrometry (GC-MS). To determine the IC 50 of the oil, the cellular viability curve and the inhibitory effects were measured by means of the oil’s association with Fluconazole in a broth microdilution assay with spectrophotometric readings. The Minimum Fungicidal Concentration (MFC) was determined by solid medium subculture with the aid of a guide plate while the assays used to verify morphological changes emerging from the action of the fractions were performed in microculture chambers at concentrations based on the microdilution. Two major oil constituents stand out from the chemical analysis: selina-1,3,7(11)-trien-8-one (36.37%) and selina-1,3,7(11)-trien-8-one epoxide (27.32%). The concentration that reduced microorganismal growth was ≥8,192 μg/mL while the IC 50 varied, this being between 1892.47 and 12491.80 μg/mL (oil), 10.07 – 80.78 μg/mL (fluconazole) and 18.53 – 295.60 μg/mL (fluconazole + oil). The combined activity (fluconazole + oil) resulted in indifference and antagonism. A MFC of the oil in association with fluconazole was recorded at the concentration of 8,192 μg/mL against CA and CK. The oil caused the inhibition of CA and CT morphological transition. In view of the results obtained, additional research is needed to elucidate the activity of the E. uniflora oil over genetic and biochemical processes regarding its effect on Candida spp. virulence. [ABSTRACT FROM AUTHOR]

Candidiasis is an infectious disease caused by some fungi of the genus Candida. In Brazil, the incidence rate is higher than in European countries and the United States, and health problems occur mainly due to the virulence factors of the fungi, which have made treatment with commercial drugs difficult. Considering the context, plants rich in phenolic compounds, such as those of the genus Piper, have been studied due to their antimicrobial properties. Thus, the objective of this study was to isolate and characterize the essential oil of Piper rivinoides Kunth, as well as to analyze the bioactivity of this essential oil and the myristicin and elemicin isolates against opportunistic fungal pathogens. The broth microdilution method was used to identify the intrinsic activity of the isolated natural products alone and combined with fluconazole to obtain the 50 % inhibitory concentration of the fungi (IC 50 ). Microdilution subculture assays were performed to determine the minimum fungicidal concentration. The results revealed moderate antifungal activity of P. rivinoides oil against C. tropicalis (512 μg/mL), C. albicans (1024 μg/mL), and P. kudriavzevii (512 μg/mL). Myristicin also showed moderate activity against C. albicans, C. tropicalis and P. kudriavzevii at 1024 μg/mL. As for elemicin, inhibition occurred at a concentration of 512 μg/mL for both strains, except against P. kudriavzevii, which was from 128 μg/mL. Combined with fluconazole, the products modified the drug's action, increasing its efficacy at concentrations ranging from 0.007 to 20.78 μg/mL, except for elemicin, which antagonized the drug's effect, modifying its action from 32.17 to 74.18 μg/mL against P. kudriavzevii. The antifungal effect of compounds, alone or in combination with fluconazole, was fungistatic, except for P. kudriavzevii, which was fungicidal in the isolated test with elemicin at concentrations starting from 128 μg/mL. Therefore, P. rivinoides and its isolated compounds have the potential for combination therapy with antifungals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)