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Medicinal Chemistry Research

, Volume 24, Issue 5, pp 1799–1813 | Cite as

Comparison of anti-Candida albicans activities of halogenomethylsulfonyl derivatives

  • Małgorzata Bondaryk
  • Zbigniew Ochal
  • Monika StaniszewskaEmail author
Original Research

Abstract

A rapidly growing resistance of Candida spp. requires a search for bioactive compounds with fungicidal or fungistatic activity. In this context a characteristics and comparison of antifungal properties of 19 sulfone derivatives were conducted. MICs of the Compounds were determined using the M27-A3 protocol following CLSI recommendations. The SAP expression was analyzed using RT-PCR; relative quantification was normalized against ACT1 in cells grown in YEPD and on Caco-2. 79 % of sulfone derivatives (15 out of 19) exhibited an activity against Candida albicans in the tested concentrations. While the addition of both chlorine and bromine atoms to halogenomethylsulfonyl groups stimulates sulfone’s antifungal activity, a chlorine atom more effectively up-regulates antifungal properties of the tested sulfones. The insertion of a fluorine atom has a binary effect on antifungal properties of the tested sulfones. The fluorine atom enhances anti-Candida properties when introduced to the aromatic ring, while its presence in halogenomethylsulfonyl group generally lowers the Compound’s efficiency. The deletion of particular SAP genes resulted in an increased susceptibility of C. albicans toward sulfones indicating the role of this gene family in resistance mechanisms. Furthermore, RT-PCR analysis demonstrated that sulfone derivatives inhibit the SAP2 expression but not that of SAP7.

Keywords

Candida albicans Resistance SAP Sulfone derivatives 

Abbreviations

CLSI

Clinical Laboratory Standards Institute

DMSO

Dimethyl sulfoxide

EMEM

Eagle’s minimum essential medium

FCS

Fetal calf serum

MIC

Minimal inhibitory concentration

PBS

Phosphate-based saline

RPMI 1640

Roswell Park Memorial Institute Medium

RT-PCR

Reverse transcription polymerase chain reaction

SAP

Secreted aspartic proteases

YEPD

Yeast extract-peptone-dextrose growth medium

XTT

Sodium 3′ -[1-(phenylaminocarbonyl)- 3,4-tetrazolium]-bis (4-methyloxy-6-nitro) benzene sulfonic acid hydrate

Notes

Acknowledgments

The work was supported by the research project of the National Science Centre, Project DEC-2011/03/D/NZ7/06198. We are extremely grateful to many colleagues and all the individuals who were generous with their advice, and provided us with strains and reagents; Professor Hsiu-Jung Lo from National Health Research Institute in Zhunan (Taiwan) with the following strains: Can16, YLO323, HLC52, HLC54, HLC74, and HLC84; Professor Joachim Morschhäuser from University of Würzburg (Germany) with following strains: SAP1MS4B, SAP2MS4B, SAP12MS4B, SAP13MS4B, SAP23MS4C, SAP3MS4B, SAP4MS4B, SAP5MS4B, SAP6MS4B, and SAP456MS4B.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Małgorzata Bondaryk
    • 1
  • Zbigniew Ochal
    • 2
  • Monika Staniszewska
    • 1
    Email author
  1. 1.Independent Laboratory of Streptomyces and Fungi ImperfectiNational Institute of Public Health-National Institute of HygieneWarsawPoland
  2. 2.Faculty of ChemistryWarsaw University of TechnologyWarsawPoland

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