Promising synergistic activity of fluconazole with bioactive Guttiferone-A and derivatives against non-albicans...

Natural products with diverse bioactivities and structures are an important source of novel chemicals with pharmaceutical potentials. Combinations of bioactive compounds with classical antimicrobial agents against drug-resistant or low-susceptible Candida spp. have been studied. Guttiferone-A and its derivatives were combined with fluconazole through the checkerboard method and tested against Candida spp. The results obtained, especially the Fractional Inhibitory Concentration Index (FICI) determined to the combinations, suggests promising results on the treatment of Candida infections, principally for species that present resistance or low antifungal susceptibility. The best result was seen for C. krusei, in which a synergic action of the association between fluconazole and Guttiferone-A resulted in a reduction of more than 100-fold in the alone inhibitory concentration (MIC) of fluconazole. Synergism was also noted in the association of fluconazole with the synthetic derivatives LFQM-79, LFQM-80 and LFQM-81 against C. glabrata, with reduction of up to four times in the alone IC of fluconazole. These results suggest the possibility of combined administration with reduction of doses and side effects of drugs conventionally used against Candida spp. and the promising therapeutic action of Guttiferone-A.