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

Ła̧cka I, Konieczny MT, Bułakowska A, Kodedová M, Gašková D, Maurya IK, Prasad R, Milewski S - Front Microbiol (2015)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology Gdańsk, Poland.

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).

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: Selected chalcones 6, 11, 18, and 21 were tested in a broad range of concentrations, from 0.1 μM to 20 μM. The representative staining curves obtained for chalcone derivatives are presented in Figure 1. Cells treated with 11 (Figure 1A) demonstrated the highest initial rate of staining, indicating rapidly increasing cell surface permeability for the probe. It should be noted that the magnitude of the red shift induced by 11 action on AD1-3 cells (drug efflux pump-free) was concentration-dependent and was observed even at concentration as low as 0.1 μM (graphs not shown). Addition of the CD cocktail caused lower drop of λmax, indicating partial cell damage.


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

Ła̧cka I, Konieczny MT, Bułakowska A, Kodedová M, Gašková D, Maurya IK, Prasad R, Milewski S - Front Microbiol (2015)

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.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525051&req=5

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.
Mentions: Selected chalcones 6, 11, 18, and 21 were tested in a broad range of concentrations, from 0.1 μM to 20 μM. The representative staining curves obtained for chalcone derivatives are presented in Figure 1. Cells treated with 11 (Figure 1A) demonstrated the highest initial rate of staining, indicating rapidly increasing cell surface permeability for the probe. It should be noted that the magnitude of the red shift induced by 11 action on AD1-3 cells (drug efflux pump-free) was concentration-dependent and was observed even at concentration as low as 0.1 μM (graphs not shown). Addition of the CD cocktail caused lower drop of λmax, indicating partial cell damage.

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology Gdańsk, Poland.

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).

No MeSH data available.


Related in: MedlinePlus