Faculty of Chemistry Repository - Cherry
University of Belgrade - Faculty of Chemistry
    • English
    • Српски
    • Српски (Serbia)
  • English 
    • English
    • Serbian (Cyrillic)
    • Serbian (Latin)
  • Login
View Item 
  •   Cherry
  • Hemijski fakultet
  • Publikacije
  • View Item
  •   Cherry
  • Hemijski fakultet
  • Publikacije
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction

Authorized Users Only
2018
Authors
Lazić, Jelena O.
Ajdačić, Vladimir
Vojnović, Sandra
Zlatović, Mario
Pekmezović, Marina
Mogavero, Selene
Opsenica, Igor
Nikodinović-Runić, Jasmina
Article (Published version)
Metadata
Show full item record
Abstract
Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activati...on of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.

Keywords:
Antifungal activity / Candida spp. / Bis-guanylhydrazone / DNA interaction / ROS generation / Synergy
Source:
Applied Microbiology and Biotechnology, 2018, 102, 4, 1889-1901
Publisher:
  • Springer, New York
Funding / projects:
  • The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
  • Microbial diversity study and characterization of beneficial environmental microorganisms (RS-173048)
  • OPATHY - From Omics to Patient: Improving Diagnostics of Pathogenic Yeasts (EU-642095)
  • European Unions Horizon research and innovation program under the Marie Sklodowska-Curie Grant [642095]
  • European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Note:
  • Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3176

DOI: 10.1007/s00253-018-8749-3

ISSN: 0175-7598

PubMed: 29330691

WoS: 000424053700030

Scopus: 2-s2.0-85041438337
[ Google Scholar ]
8
7
URI
https://cherry.chem.bg.ac.rs/handle/123456789/2078
Collections
  • Publikacije
  • Publikacije
Institution/Community
Hemijski fakultet
TY  - JOUR
AU  - Lazić, Jelena O.
AU  - Ajdačić, Vladimir
AU  - Vojnović, Sandra
AU  - Zlatović, Mario
AU  - Pekmezović, Marina
AU  - Mogavero, Selene
AU  - Opsenica, Igor
AU  - Nikodinović-Runić, Jasmina
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2078
AB  - Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.
PB  - Springer, New York
T2  - Applied Microbiology and Biotechnology
T1  - Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction
VL  - 102
IS  - 4
SP  - 1889
EP  - 1901
DO  - 10.1007/s00253-018-8749-3
UR  - Kon_3409
ER  - 
@article{
author = "Lazić, Jelena O. and Ajdačić, Vladimir and Vojnović, Sandra and Zlatović, Mario and Pekmezović, Marina and Mogavero, Selene and Opsenica, Igor and Nikodinović-Runić, Jasmina",
year = "2018",
abstract = "Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.",
publisher = "Springer, New York",
journal = "Applied Microbiology and Biotechnology",
title = "Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction",
volume = "102",
number = "4",
pages = "1889-1901",
doi = "10.1007/s00253-018-8749-3",
url = "Kon_3409"
}
Lazić, J. O., Ajdačić, V., Vojnović, S., Zlatović, M., Pekmezović, M., Mogavero, S., Opsenica, I.,& Nikodinović-Runić, J.. (2018). Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. in Applied Microbiology and Biotechnology
Springer, New York., 102(4), 1889-1901.
https://doi.org/10.1007/s00253-018-8749-3
Kon_3409
Lazić JO, Ajdačić V, Vojnović S, Zlatović M, Pekmezović M, Mogavero S, Opsenica I, Nikodinović-Runić J. Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. in Applied Microbiology and Biotechnology. 2018;102(4):1889-1901.
doi:10.1007/s00253-018-8749-3
Kon_3409 .
Lazić, Jelena O., Ajdačić, Vladimir, Vojnović, Sandra, Zlatović, Mario, Pekmezović, Marina, Mogavero, Selene, Opsenica, Igor, Nikodinović-Runić, Jasmina, "Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction" in Applied Microbiology and Biotechnology, 102, no. 4 (2018):1889-1901,
https://doi.org/10.1007/s00253-018-8749-3 .,
Kon_3409 .

DSpace software copyright © 2002-2015  DuraSpace
About CHERRY - CHEmistry RepositoRY | Send Feedback

re3dataOpenAIRERCUB
 

 

All of DSpaceInstitutions/communitiesAuthorsTitlesSubjectsThis institutionAuthorsTitlesSubjects

Statistics

View Usage Statistics

DSpace software copyright © 2002-2015  DuraSpace
About CHERRY - CHEmistry RepositoRY | Send Feedback

re3dataOpenAIRERCUB