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. 2015 Aug 5:6:783.
doi: 10.3389/fmicb.2015.00783. eCollection 2015.

Chemosensitization of multidrug resistant Candida albicans by the oxathiolone fused chalcone derivatives

Izabela Ła̧cka  1 , Marek T Konieczny  2 , Anita Bułakowska  2 , Marie Kodedová  3 , Dana Gašková  3 , Indresh K Maurya  4 , Rajendra Prasad  4 , Sławomir Milewski  1
Affiliations

Chemosensitization of multidrug resistant Candida albicans by the oxathiolone fused chalcone derivatives

Izabela Ła̧cka et al. Front Microbiol. .

Abstract

Three structurally related oxathiolone fused chalcone derivatives appeared effective chemosensitizers, able to restore in part sensitivity to fluconazole of multidrug-resistant C. albicans strains. Compound 21 effectively chemosensitized cells resistant due to the overexpression of the MDR1 gene, compound 6 reduced resistance of cells overexpressing the ABC-type drug transporters CDR1/CDR2 and derivative 18 partially reversed fluconazole resistance mediated by both types of yeast drug efflux pumps. The observed effect of sensitization of resistant strains of Candida albicans to fluconazole activity in the presence of active compounds most likely resulted from inhibition of the pump-mediated efflux, as was revealed by the results of studies involving the fluorescent probes, Nile Red, Rhodamine 6G and diS-C3(3).

Keywords: Candida albicans; antifungals; chalcones; chemosensitization; multidrug resistance.

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Figures

Figure 1
Figure 1
Effect of selected compounds on the membrane potential and activity of MDR pumps of S. cerevisiae. Staining curves of AD1-3 (squares), AD23 (diamonds), AD12 (circles), AD13 (inverted triangles), and US50-18C (triangles) cells. Empty symbols–no compound added; full symbols–compounds added 10 min before diS-C3(3) at following concentrations: 1 μM (A), 10 μM (B–D). Dotted lines with arrows indicate the addition of the CD cocktail.
Figure 2
Figure 2
Influence of selected chalcones on Nile Red accumulation in drug efflux pump-free and MDR yeast cells. Cells were incubated for 30 min with Nile Red and chalcones and then fluorescence was measured with a flow cytometer. Values are the means of three independent experiments. Bars represent SD.
Figure 3
Figure 3
Changes in the cell surface of C. albicans cells observed by transmission electron microscopy: (A) control cells; (B–D) cells treated with 11, 10 μg/mL, for 3, 6, and 9 h.
Figure 4
Figure 4
Structures of chemosensitizers of MDR yeasts selected in this study.
See this image and copyright information in PMC

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