In Vivo Antileishmanial Effect of 3,5-Diaryl-isoxazole Analogues Based on Veraguensin, Grandisin, and Machilin G: A Glance at a Preclinical Study.

New treatment approaches targeting cutaneous leishmaniasis (CL) are required since conventional drugs exhibit limitations due to their several adverse effects and toxicity. In this study, we aimed to evaluate the in vivo intralesional treatment efficacy of five isoxazole derivatives previously synthesized and effective in vitro against intracellular amastigote forms of Leishmania (L.) amazonensis. Among the tested analogues, 7 exhibited relevant in vivo therapeutic effects. The in silico predictions provided interesting information about the toxicity, suggesting the safety of analogue 7. Experiments performed with Salmonella typhimurium strains (TA98, TA100, and TA102) showed a non-mutagenicity profile of 7. The treatment of Leishmania-infected BALB/c mice with isoxazole 7 showed remarkably smaller CL lesions and decreased the parasitism (by 98.4%) compared to the control group. Hence, analogue 7 is a promising drug candidate and alternative treatment for CL caused by L. amazonensis.

Silver nanoparticles stabilized with propolis show reduced toxicity and potential activity against fungal infections.

Aim: Elucidate the antifungal efficacy of biologically synthesized silver nanoparticles with ethanolic propolis extract (AgNPs PE) against the planktonic forms and biofilms of clinically important fungi. Materials & methods: AgNPs were synthesized, characterized and evaluated for cytotoxicity, mutagenicity and antimicrobial activity. Results: AgNPs PE displayed a colloidal appearance, good stability and size of 2.0-40.0 nm. AgNPs PE demonstrated lower cytotoxicity and nonmutagenic potential. In addition, AgNPs PE displayed antifungal properties against all tested isolates, inhibiting growth at concentrations lower than the cytotoxic effect. Mature biofilms treated for 48 h with AgNPs PE showed significant reduction of viable cells, metabolic activity and total biomass. Conclusion: This is the first time that AgNPs have been synthesized from an ethanolic extract of propolis only, proving antifungal, antibiofilm, atoxic and nonmutagenic properties.

Propolis extract has bioactivity on the wall and cell membrane of Candida albicans.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of natural products such as propolis extract (PE) is a promising alternative when topically administered to replace conventional antifungals, mostly due to its therapeutic applications, ease of access and low toxicity. However, despite being the subject of several mycology studies, they focus primarily on exploiting their antimicrobial activity, lacking information on the mechanisms of action of PE on Candida spp., characterizing its antifungal potential. AIM OF THE STUDY: To elucidate the bioactivity of PE on the cellular structure of Candida albicans. MATERIALS AND METHODS: A total of seven C. albicans clinical isolates plus a reference strain of C. albicans ATCC 90028 were used in this study. The PE was characterized and its effect on C. albicans was determined by susceptibility and growth kinetics assays; interference on C. albicans germination and filamentation; evaluation of the integrity of the C. albicans cell wall and membrane, as well as its mutagenic potential. RESULTS: The PE presented strong inhibitory activity, which showed its greatest antifungal activity at 12 h with dose and time dependent fungistatic characteristics, effectively inhibiting and interfering on C. albicans filamentation. In addition, PE caused membrane and cell wall damage with intracellular content extravasation. Moreover, PE was not mutagenic. CONCLUSIONS: The bioactivity of PE is mainly related to the loss of integrity membrane as well as the integrity of the cell wall and consequent increase in permeability, without mutagenic effects.