Guanidine alkaloids reverse the fluconazole resistance phenotype mediated by Pdr5p transporter on Saccharomyces cerevisiae
Five years ago, Dr. Mario F. C. Santos performed a detailed investigation of the chemistry of the marine sponge Monanchora aff. arbuscula, collected in Cabo Frio, Rio de Janeiro state. Dr. Mario isolated a series of guanidine secondary metabolites, among which batzelladine D (1) and norbatzelladine L (2) were two of the major alkaloids. This first chemical investigation resulted in the discovery of several new alkaloids, along with the total synthesis of monalidine and the report of anti-leishmanial and anti-Chagas disease activity of these compounds. These first results have been published in the Journal of Natural Products.
More recently the group of our collaborator at the Universidade Federal do Rio de Janeiro, Professor Antonio Ferreira-Pereira, investigated the antifungal mechanism of action of batzelladine D (1) and norbatzelladine L (2). His research group demonstrated that both alkaloids 1 and 2 reverse the fluconazole resistance phenotype mediated by Pdr5p transporter on Saccharomyces cerevisiae. Both alkaloids were able to chemosensitize the Pdr5p-overexpressing strain by synergistic interaction with fluconazole, and also showed inhibitory effect on the catalytic activity and on the intracellular accumulation of rhodamine 6G, with no significant in vitro mammalian cells toxicity. These results have been recently published in the journal Bioorganic Chemistry, and can be read here.
