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

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Abstract

Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro. Most of these compounds showed good synergistic activities against C. tropicalis. Among them, compound 9 exhibited significant synergistic activities against Candida spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 μg ml−1 fluconazole and 64 μg ml−1 or 128 μg ml−1 compound 9 showed the most potent fungicidal effect against C. tropicalis. 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.

Graphical abstract: Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.

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Publication details

The article was received on 22 Nov 2016, accepted on 16 Mar 2017 and first published on 17 Mar 2017


Article type: Research Article
DOI: 10.1039/C6MD00649C
Citation: Med. Chem. Commun., 2017, Advance Article
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    Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.

    F. Zhao, H. Dong, Y. Wang, T. Wang, Z. Yan, F. Yan, D. Zhang, Y. Cao and Y. Jin, Med. Chem. Commun., 2017, Advance Article , DOI: 10.1039/C6MD00649C

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