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The scarce antifungal arsenal, changes in the susceptibility profile of fungal agents, and lack of adherence to treatment have contributed to the increase of cases of dermatomycoses. In this context, new antimicrobial substances have gained importance. Chalcones are precursors of the flavonoid family that have multiple biological activities, have high tolerability by humans, and easy synthesis. In this study, we evaluated the in vitro antifungal activity, alone and in combination with conventional antifungal drugs, of the VS02–4′ethyl chalcone-derived compound against dermatophytes and Candidaspp. Susceptibility testing was carried out by broth microdilution. Experiments for determination of the target of the compound on the fungal cell, time-kill kinetics, and toxicity tests in Galleria mellonellamodel were also performed. Combinatory effects were evaluated by the checkerboard method. Results showed high activity of the compound VS02–4′ethyl against dermatophytes (MIC of 7.81–31.25 μg/ml). The compound targeted the cell membrane, and the time-kill test showed the compound continues to exert gradual activity after 5 days on dermatophytes, but no significant activity on Candida. Low toxicity was observed at 250 mg/kg. Excellent results were observed in the combinatory test, where VS02–4′ethyl showed synergistic interactions with itraconazole, fluconazole, terbinafine, and griseofulvin, against all isolates tested. Although further investigation is needed, these results revealed the great potential of chalcone-derived compounds against fungal infections for which treatments are long and laborious.

Onychomycosis is a nail infection caused by dermatophytes, non-dermatophyte fungi, and yeasts, especially Candidaspecies. The present study evaluated the combinatorial effect of different cultured extracts of Candida parapsilosisand Trichophyton mentagrophytesand Trichophyton rubrumwith fluconazole, itraconazole, and terbinafine against clinical isolates of Trichophyton rubrum. In addition, investigation of the action of the extracts on the wall or membrane was performed. Pure and mixed cultures of Candida parapsilosisand dermatophytes were filtered through a 0.2-μm membrane and submitted to liquid–liquid extraction using ethyl acetate. After a checkerboard, trial with drugs was performed to evaluate the synergistic interaction with the extract. The results obtained for the minimum inhibitory concentration (MIC) of extracts against the T. rubrumstrain in isolation were 500–8000 μg/mL. The MIC range for fluconazole, itraconazole, and terbinafine were 2–32 μg/mL, 0.25–0.5 μg/mL, 0.03–64 μg/mL, respectively. However, when the extract was combined with drugs, the MIC values decreased: extracts 1.9–1000 μg/mL, fluconazole 0.25–4, itraconazole 0.03–0.06 μg/mL, and terbinafine 0.001–0.02 μg/mL. The MIC values of the extracts in the Roswell Park Memorial Institute 1640 medium (RPMI) supplemented with sorbitol did not change, suggesting any action on the cell wall. However, in the presence of RPMI supplemented with ergosterol, MIC values of the extracts increased by up to 2×, indicating action on the fungal cell membrane. A synergistic action was observed between products and drugs, detecting a decrease in MIC values. There is potential and a new therapeutic perspective for fungal control.

Aim:This work aimed to evaluate the activity of 3′-hydroxychalcone against Cryptococcus gattiiin planktonic and biofilm forms and their toxicity using alternative animal models. Materials & methods:Minimum inhibitory concentration and minimum fungicide concentration were determined. Biofilm formation and the susceptibility tests were performed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-5-[carbonyl(phenylamino)]-2H-tetrazolium hydroxide assay. Toxicity and efficacy were checked in Danio rerioand Galleria mellonellamodels. Results:The compound 3′-hydroxychalcone showed fungicidal activity against C. gattiiin both planktonic and biofilm forms. The toxicity in zebrafish embryos revealed a low lethal concentration. In G. mellonella, the compound did not show antifungal activity and larvae toxicity. Conclusion:Because of the activity of 3′-hydroxychalcone against C. gattii in vitro, molecular modifications should be made to improve efficacy and to reduce toxicity in vivo.

The present investigation deals with the antibiotic activity of eight natural guanidine alkaloids and two synthetic analogues against a variety of clinically relevant methicillin-resistant Staphylococcus aureusstrains. Galegine (1) and pterogynidine (2) were the most potent compounds, with a minimum inhibitory concentration of 4 mg/L, to all tested strains. The preliminary chemical features correlating to anti-MRSA activity showed that the size of the side chain and the substitution pattern in the guanidine core played a key role in the antibacterial activity of the imino group. Guanidine alkaloids 1and 2are promising molecular models for further synthetic derivatives and, thus, for medicinal chemistry studies.

Xylarenones C−E (2−4), three new eremophilane sesquiterpenes, have been isolated from solid substrate cultures of a Camarops-like endophytic fungus isolated from Alibertia macrophylla. The structures were elucidated by analysis of spectroscopic data. Compounds were evaluated in subtilisin and pepsin protease assays, and compound 2showed potent inhibitory activity against both proteases.

As part of a bioprospecting program aimed at the discovery of potential anticancer drugs, two new guanidine-type alkaloids, nitensidines D and E (1, 2), and the known pterogynine (3), pterogynidine (4), and galegine (5), were isolated from the leaves of Pterogyne nitens. The structures of 1and 2were established on the basis of spectroscopic data interpretation. These compounds were tested against a small panel of human cancer cell lines. Compound 2exhibited cytotoxicity for HL-60 (human myeloblastic leukemia) and SF-245 (human glioblastoma) cells.