Production of More Potent Anti-Candida Labdane Diterpenes by Biotransformation Using Cunninghamella elegans.

Candida species are responsible for causing invasive candidiasis with high mortality rate and their resistance to available antifungal drugs is a major clinical challenge. Biotransformation process of the labdane diterpene ent-labd-8(17)-en-15,18-dioic acid (1) carried out with Cunninghamella elegans afforded five new derivatives (compounds 2-6). Unusual regioselective hydroxylation of the methyl group at the C-20 position of labdane-type diterpene was achieved and all compounds were subjected to cytotoxicity and antifungal evaluations. Compound 1 and its derivatives were not cytotoxic to normal (MCF-10A) and tumor (MCF-7) cell lines. Compounds 2 and 3 exhibited fungistatic activity against all tested Candida strains at lower concentrations than fluconazole. Both compounds also showed the strongest fungicidal activity against C. albicans, which is the most prevalent fungal agent involved in candidemia.

In vitro bioassay guided anti-dermatophyte and cytotoxic activities from Piper umbellatum L. Miq. led to 4-nerolidylcatechol.

Dermatophytosis is a dermic disease caused by fungi. The aim of this study was to search anti-dermatophyte bioactive compounds in Piper umbellatum leaves. Cytotoxicity evaluation was performed against MRC-5 and HepG2 as a selectivity parameter. Crude ethanol extract presented MIC value of 39.1 µg/mL against M. canis and no cytotoxicity to Hep G2 (human liver cancer) and MRC-5 (normal lung fibroblast). 4-nerolydilcatechol was isolated from P. umbellatum ethanolic extract. MIC values for 4-NC were 7.6µM to M. canisand 15.6µM to Trichophyton rubrum. 4-NC presented activity against M. canis14 times lower than to MRC-5 (non-tumoral human cell line), which suggest selective activity for this fungus. Molecular modeling suggests 4-NC could bind to CYP51, present in lanosterol synthesis, blocking fungi development. In conclusion, P. umbellatum crude ethanol extract and 4-NC demonstrated high and selective in vitro antifungal activity.[Formula: see text].

Flavonoids from Plinia cauliflora (Mart.) Kausel (Myrtaceae) with antifungal activity.

Plinia cauliflora is a plant species with edible fruits but its chemical composition is not totally known yet although former studies showed its potential as antifungal agent. This work aimed the chemical analysis of the leaves, the activity against fungi species and evaluated cytotoxicity. Extract was obtained with 70% ethanol. An ethyl acetate fraction was obtained and glycosylated quercetin and myricetin were isolated. Samples were tested against Candida species, dermatophytes and entomopathogenic fungi. Cytotoxicity was evaluated against fibroblast cells. Extract showed good activity against C. albicans (minimum inhibitory concentration at 156 µg/mL), C. parapsilosis (78 µg/mL), C. krusei (19 µg/mL), Trichophyton rubrum (78 µg/mL) and Microsporum canis (156 µg/mL). Isolated compounds were more active against C. krusei and T. rubrum. The extract, which was the more active sample, demonstrated low cytotoxic effect and encourage more studies against rising non-albicans species and dermatophyte T. rubrum.

Antifungal, antiradical and cytotoxic activities of extractives obtained from Tagetes patula L. (Asteraceae), a potential acaricide plant species.

Tagetes patula L. shows a complex chemical composition, ranging from glycosylated flavonoids and thiophenes in extracts until terpenoids in the essential oil. In the present study, due to this rich flavonoidic constitution, its antioxidant potential was determined, having shown values of antiradical percentage superior to reference compounds, mainly the extracts prepared with flowers. Previous studies performed emphasized the acaricide potential of T. patula and thus, the present study aimed to verify the action of extractives obtained from aerial parts on growth of entomopathogenic fungi related to biological control of brown dog tick Rhipicephalus sanguineus and the action against pathogenic fungi closely associated with pets. None of the samples inhibited the growth of strains of Beauveria bassiana or Metarhizium anisopliae, enabling feasible future studies of synergism on acaricide activity of formulations containing fungi and extracts. The antimicrobial activity of ethanolic extract of flowers (FlEtOH70%) against Microsporum canis and Trichophyton rubrum was significant (193.3 µg/mL and 253.9 µg/mL, respectively), as well as ethanolic extract from aerial parts (APEtOH70%) against T. rubrum (312.5 µg/mL). In order to ensure the safety of a topical formulation containing the extractives of T. patula, the cytotoxic potential of these samples were tested in murine macrophages cells. At higher concentrations all extracts were quite lethal, with IC50 ranging from 210.96 µg/mL to 468.75 µg/mL for APEtOH70% and FlEtOH70%, respectively. These results suggest that the application of a product containing T. patula extractives in the control of ticks could be used, at principle, only on the environment.