amphotericin-b and caffeic-acid

Cryptococcus neoformans/Cryptococcus gattii complex species are etiological agents of cryptococcosis, a systemic mycosis that cause respiratory infection and meningoencephalitis. To establish the infection, these yeasts produce virulence factors, such as melanin, which contribute to pathogenicity and antifungal tolerance. The aim of this study was to investigate melanin production by the C. neoformans/C. gattii complex in the presence of different precursors of melanogenesis and evaluate the effect of melanization on the antifungal susceptibility of these species to fluconazole, flucytosine and amphotericin B. Epinephrine, norepinephrine, dopamine and caffeic acid were used as substrates for melanin production, and l-dopa was used as positive control. The susceptibility of melanized strains (n = 6), after exposure to epinephrine or l-dopa, was evaluated by broth microdilution assay, and non-melanized strains were used as control. The antifungal activity of amphotericin B against melanized strains was also investigated by time kill assay. All Cryptococcus spp. strains produced melanin after exposure to the tested substrates. After exposure to epinephrine, minimum inhibitory concentration (MIC) ranges were 1-8 μg/mL for fluconazole, 2-8 μg/mL for flucytosine and 0.125-1 μg/mL for amphotericin B, while, after exposure to l-dopa, MIC ranges were 2-8 μg/mL for fluconazole, 4-8 μg/mL for flucytosine, and 0.125-0.5 μg/mL for amphotericin B. Similar results were observed for non-melanized strains. The production of melanin after exposure to epinephrine was higher than that induced by l-dopa. Melanized cells of both species were more tolerant to amphotericin B than the non-melanized control, emphasizing the importance of melanin production for fungal virulence.

Topics: Amphotericin B; Animals; Anti-Bacterial Agents; Antifungal Agents; Caffeic Acids; Cryptococcus gattii; Cryptococcus neoformans; Dopamine; Epinephrine; Humans; Melanins; Microbial Sensitivity Tests; Norepinephrine

The synthesis, cytotoxicity, anti-leishmanial and anti-trypanosomal activities of twelve triclosan-caffeic acid hybrids are described herein. The structure of the synthesized products was elucidated by a combination of spectrometric analyses. The synthesized compounds were evaluated against amastigotes forms of L. (V) panamensis, which is the most prevalent Leishmania species in Colombia, and against Trypanosoma cruzi, which is the pathogenic species to humans. Cytotoxicity was evaluated against human U-937 macrophages. Eight compounds were active against L. (V) panamensis (18-23, 26 and 30) and eight of them against T. cruzi (19-22, 24 and 28-30) with EC

Topics: Antiprotozoal Agents; Caffeic Acids; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Humans; Leishmania; Macrophages; Molecular Structure; Parasitic Sensitivity Tests; Structure-Activity Relationship; Triclosan; Trypanosoma cruzi