Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant spp.

Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant spp. The minimal inhibitory concentration (MIC) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant , and . Most of these compounds showed good synergistic activities against . Among them, compound exhibited significant synergistic activities against spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 μg ml fluconazole and 64 μg ml or 128 μg ml compound showed the most potent fungicidal effect against . The synergistic effect may be associated with the changes of the intracellular ATP content and cell membrane permeability. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for fluconazole-resistant candidiasis.