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Aryl-alkyl-lysines: Membrane-Active Fungicides That Act against Biofilms of Candida albicans.

Publication ,  Journal Article
Ghosh, C; Yadav, V; Younis, W; Mohammad, H; Hegazy, YA; Seleem, MN; Sanyal, K; Haldar, J
Published in: ACS infectious diseases
April 2017

Mortality due to pathogenic fungi has been exacerbated by the rapid development of resistance to frontline antifungal drugs. Fungicidal compounds with novel mechanisms of action are urgently needed. Aryl-alkyl-lysines, which are membrane-active small molecules, were earlier shown to be broad-spectrum antibacterial agents with potency in vitro and in vivo. Herein, we report the antifungal properties of aryl-alkyl-lysines. After identifying the most active compound (NCK-10), we tested its activity against a panel of clinically relevant pathogenic fungi and examined NCK-10's effect against immature and mature biofilms of Candida albicans. NCK-10 was capable of inhibiting the growth of various species of fungi (including Candida spp., Cryptococcus spp., and Aspergillus fumigatus) at concentrations similar to those of antifungal drugs used clinically. It was observed that polarization and permeability of the fungal cell membrane were compromised upon addition of NCK-10, indicating its mechanism is disruption of the fungal cell membrane. In addition to interfering with the growth of planktonic fungi, NCK-10 demonstrated the ability to both inhibit biofilm formation and reduce the metabolic activity of cells in C. albicans biofilm. Additionally, our compound was capable of crossing the blood-brain barrier in an in vitro model, expanding the potential antifungal applications for NCK-10. Overall, aryl-alkyl-lysines were found to be excellent compounds that warrant further investigation as novel antifungal agents.

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Published In

ACS infectious diseases

DOI

EISSN

2373-8227

ISSN

2373-8227

Publication Date

April 2017

Volume

3

Issue

4

Start / End Page

293 / 301

Related Subject Headings

  • Peptidomimetics
  • Microbial Sensitivity Tests
  • Humans
  • Cell Membrane Permeability
  • Cell Membrane
  • Candida albicans
  • Biofilms
  • Antifungal Agents
  • 3207 Medical microbiology
  • 1108 Medical Microbiology
 

Citation

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Ghosh, C., Yadav, V., Younis, W., Mohammad, H., Hegazy, Y. A., Seleem, M. N., … Haldar, J. (2017). Aryl-alkyl-lysines: Membrane-Active Fungicides That Act against Biofilms of Candida albicans. ACS Infectious Diseases, 3(4), 293–301. https://doi.org/10.1021/acsinfecdis.6b00192
Ghosh, Chandradhish, Vikas Yadav, Waleed Younis, Haroon Mohammad, Youssef A. Hegazy, Mohamed N. Seleem, Kaustuv Sanyal, and Jayanta Haldar. “Aryl-alkyl-lysines: Membrane-Active Fungicides That Act against Biofilms of Candida albicans.ACS Infectious Diseases 3, no. 4 (April 2017): 293–301. https://doi.org/10.1021/acsinfecdis.6b00192.
Ghosh C, Yadav V, Younis W, Mohammad H, Hegazy YA, Seleem MN, et al. Aryl-alkyl-lysines: Membrane-Active Fungicides That Act against Biofilms of Candida albicans. ACS infectious diseases. 2017 Apr;3(4):293–301.
Ghosh, Chandradhish, et al. “Aryl-alkyl-lysines: Membrane-Active Fungicides That Act against Biofilms of Candida albicans.ACS Infectious Diseases, vol. 3, no. 4, Apr. 2017, pp. 293–301. Epmc, doi:10.1021/acsinfecdis.6b00192.
Ghosh C, Yadav V, Younis W, Mohammad H, Hegazy YA, Seleem MN, Sanyal K, Haldar J. Aryl-alkyl-lysines: Membrane-Active Fungicides That Act against Biofilms of Candida albicans. ACS infectious diseases. 2017 Apr;3(4):293–301.
Journal cover image

Published In

ACS infectious diseases

DOI

EISSN

2373-8227

ISSN

2373-8227

Publication Date

April 2017

Volume

3

Issue

4

Start / End Page

293 / 301

Related Subject Headings

  • Peptidomimetics
  • Microbial Sensitivity Tests
  • Humans
  • Cell Membrane Permeability
  • Cell Membrane
  • Candida albicans
  • Biofilms
  • Antifungal Agents
  • 3207 Medical microbiology
  • 1108 Medical Microbiology