Discovery of the rapanone and suberonone mixture as a motif for leishmanicidal and antifungal applications.

Leishmaniasis and fungal infections are significant diseases impacting worldwide public health. Treatments have developed greatly over time, however, there is a necessity to discover less toxic drugs, which have greater efficacy and are more economically accessible. This work conducted a screening of Cerrado species extracts: Connarus suberosus Planch. (Connaraceae), Neea theifera Oerst. (Nyctaginaceae) and Myrcia linearifolia Cambess. (Myrtaceae) against Leishmania (Leishmania) amazonensis, dermatophytes and yeasts. Leishmanicidal and antifungal tests were conducted using MTT colorimetric assay and CLSI methodology, respectively. Connarus suberosus extracts presented the most promising results against the aforementioned microorganisms, which has not been described in the literature. The root bark EtOAc extract was selected for chemical fractionation resulting in a mixture of rapanone (1) and a previously unreported compound named as suberonone (2); a mixture of ß-sitosterol (3) and stigmasterol (4); oleic acid (5); geranilgeraniol (6); and two derivatives obtained from 1 and 2 mixture. The rapanone and suberonone mixture demonstrated a MIC of 15.62 µg/mL against Candida albicans ATCC 10231.

Activity of Fabaceae species extracts against fungi and Leishmania: vatacarpan as a novel potent anti-Candida agent

AbstractLeishmaniasis and fungal infection treatment efficacy is limited by toxicity and ever increasing resistance to available drugs, requiring development of alternative compounds. The richness of Cerrado plant antimicrobial secondary metabolites justifies screening of Fabaceae species extracts: Enterolobium ellipticum Benth., Sclerolobium aureum (Tul.) Baill. and Vatairea macrocarpa(Benth.) Ducke, against Leishmania(Leishmania) amazonensis, yeasts and dermatophytes. Among the 26 extracts tested, more than 50% of the total demonstrated significant antifungal activity in comparison to the drug controls (minimal inhibitory concentration 0.12 to ≤31.25 µg/ml). Six extracts capable of complete parasitic growth inhibition had the inhibitory concentration index for 50% values from 9.23 to 78.65 µg/ml. The results led to the selection of the V. macrocarpa ethyl acetate root bark extract for chemical fractionation. This plant, traditionally referred to as angelim-do-cerrado or maleiteira, is used to treat superficial mycoses in Amazonia. A previously unreported pterocarpan vatacarpan together with the known compound musizin was isolated. Vatacarpan demonstrated a minimal inhibitory concentration value of 0.98 µg/ml against Candida albicans ATCC 10231, and thus comparable or superior to fluconazole and amphotericin B. The results add to literature's information the ability of pterocarpans to act as antimicrobial agents.