• English
    • Türkçe
  • English 
    • English
    • Türkçe
  • Login
View Item 
  •   DSpace Home
  • Araştırma Çıktıları / WOS
  • Araştırma Çıktıları / WOS
  • View Item
  •   DSpace Home
  • Araştırma Çıktıları / WOS
  • Araştırma Çıktıları / WOS
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies

Thumbnail
View/Open
New azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies.pdf (2.518Mb)
Date
2017
Author
Doğan, İnci Selin
Saraç, Selma
Sarı, Suat
Kart, Didem
Eşsiz, Şebnem
Vural, İmran
Dalkara, Sevim
Abstract
Azole antifungals are potent inhibitors of fungal lanosterol 14 alpha demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design synthesis and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl) ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 mu g/mL against Candida albicans. Additionally some of our compounds such as 19 (MIC: 0.25 mu g/mL) were potent against resistant C. glabrata a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. (C) 2017 Elsevier Masson SAS. All rights reserved.

Source

European Journal of Medicinal Chemistry

Volume

130

Pages

124-138

URI

https://hdl.handle.net/20.500.12469/351
https://doi.org/10.1016/j.ejmech.2017.02.035

Collections

  • Araştırma Çıktıları / PubMed [194]
  • Araştırma Çıktıları / Scopus [1565]
  • Araştırma Çıktıları / WOS [1518]
  • Biyoinformatik ve Genetik / Bioinformatics and Genetics [220]

Keywords

Azoles
Antifungal
Candida species
CYP51
Molecular docking
Molecular dynamics simulation

Share


DSpace software copyright © 2002-2015  DuraSpace
Contact Us | Send Feedback
Theme by 
@mire NV
 

 

Browse

All of DSpaceCommunities & CollectionsBy Issue DateBy AuthorsBy TitlesBy SubjectsBy TypesBy LanguagesBy DepartmentsBy PublishersBy KHAS AuthorsBy Access TypesThis CollectionBy Issue DateBy AuthorsBy TitlesBy SubjectsBy TypesBy LanguagesBy DepartmentsBy PublishersBy KHAS AuthorsBy Access Types

My Account

LoginRegister

Statistics

View Google Analytics Statistics

DSpace software copyright © 2002-2015  DuraSpace
Contact Us | Send Feedback
Theme by 
@mire NV