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

Overview of attention for article published in Applied Microbiology & Biotechnology, January 2018
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Title
Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction
Published in
Applied Microbiology & Biotechnology, January 2018
DOI 10.1007/s00253-018-8749-3
Pubmed ID
Authors

Jelena Lazić, Vladimir Ajdačić, Sandra Vojnovic, Mario Zlatović, Marina Pekmezovic, Selene Mogavero, Igor Opsenica, Jasmina Nikodinovic-Runic

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 guanidine-containing 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 bis-guanylhydrazones were between 2 and 15.6 μg/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitro DNA 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.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 24%
Student > Master 3 18%
Professor 2 12%
Student > Ph. D. Student 2 12%
Other 1 6%
Other 3 18%
Unknown 2 12%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 18%
Chemistry 3 18%
Pharmacology, Toxicology and Pharmaceutical Science 2 12%
Biochemistry, Genetics and Molecular Biology 2 12%
Business, Management and Accounting 1 6%
Other 3 18%
Unknown 3 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 August 2018.
All research outputs
#10,617,835
of 13,337,884 outputs
Outputs from Applied Microbiology & Biotechnology
#4,303
of 5,509 outputs
Outputs of similar age
#277,007
of 384,470 outputs
Outputs of similar age from Applied Microbiology & Biotechnology
#72
of 114 outputs
Altmetric has tracked 13,337,884 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 5,509 research outputs from this source. They receive a mean Attention Score of 3.6. This one is in the 14th percentile – i.e., 14% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 384,470 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 114 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.