Cyclization and unsaturation rather than isomerisation of side chains govern the selective antibacterial activity of cationic-amphiphilic polymers

2016 ◽  
Vol 52 (25) ◽  
pp. 4644-4647 ◽  
Author(s):  
D. S. S. M. Uppu ◽  
M. Bhowmik ◽  
S. Samaddar ◽  
J. Haldar
Keyword(s):  
Antibacterial Activity ◽  
Mammalian Cell ◽  
Amphiphilic Polymers ◽  
Side Chains ◽  
Cell Toxicity ◽  
Mammalian Cell Toxicity

The influence of cyclization and unsaturation on the hydrophobic side chains of cationic-amphiphilic polymers towards antibacterial activity and mammalian cell toxicity is reported.

Impact of structural changes in heteroleptic bismuth phosphinates on their antibacterial activity in Bi-nanocellulose composites

2020 ◽  
Vol 49 (22) ◽  
pp. 7341-7354 ◽  
Author(s):  
Megan E. Herdman ◽  
Melissa V. Werrett ◽  
Rebekah N. Duffin ◽  
Liam J. Stephens ◽  
Rajini Brammananth ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Mammalian Cell ◽  
Structural Changes ◽  
Cell Toxicity ◽  
Antibacterial Materials ◽  
Mammalian Cell Toxicity

A series of diphenyl mono-phosphinato bismuth complexes were synthesised to study the effect of ligand choice on antibacterial activity, mammalian cell toxicity, and their behaviour in Bi-nanocellulose composites for use as antibacterial materials.

Design of Dermaseptin S3 Analogues having Bacterial Cell Selectivity without Mammalian Cell Toxicity

2001 ◽  
Vol 8 (4) ◽  
pp. 281-288 ◽  
Author(s):  
Song Shin ◽  
Sung Yang ◽  
Soo Eom ◽  
Woo Song ◽  
Yangmee Kim ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
Bacterial Cell ◽  
Cell Toxicity ◽  
Cell Selectivity ◽  
Mammalian Cell Toxicity

Alteration of Mammalian-Cell Toxicity of Pesticides by Structural Iron(II) in Ferruginous Smectite

2004 ◽  
Vol 38 (16) ◽  
pp. 4383-4389 ◽  
Author(s):  
Kara C. Sorensen ◽  
Joseph W. Stucki ◽  
Richard E. Warner ◽  
Michael J. Plewa
Keyword(s):  
Mammalian Cell ◽  
Cell Toxicity ◽  
Structural Iron ◽  
Ferruginous Smectite ◽  
Mammalian Cell Toxicity

Dermaseptins from Phyllomedusa oreades and Phyllomedusa distincta: Secondary structure, antimicrobial activity, and mammalian cell toxicity

2008 ◽  
Vol 151 (3) ◽  
pp. 336-343 ◽  
Author(s):  
José Roberto S.A. Leite ◽  
Guilherme D. Brand ◽  
Luciano P. Silva ◽  
Selma A.S. Kückelhaus ◽  
Wilian R.C. Bento ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Secondary Structure ◽  
Mammalian Cell ◽  
Cell Toxicity ◽  
Mammalian Cell Toxicity

scholarly journals Alexidine dihydrochloride has broad spectrum a ctivities against diverse fungal pathogens

2018 ◽  
Author(s):  
Zeinab Mamouei ◽  
Abdullah Alqarihi ◽  
Shakti Singh ◽  
Shuying Xu ◽  
Michael K. Mansour ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Immunocompromised Patients ◽  
Drug Resistant ◽  
Cell Toxicity ◽  
Diverse Range ◽  
Mammalian Cell Toxicity

AbstractInvasive fungal infections due to Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, constitute a substantial threat to hospitalized, immunocompromised patients. Further, the presence of drug-recalcitrant biofilms on medical devices, and emergence of drug-resistant fungi such as Candida auris, introduce treatment challenges with current antifungal drugs. Worse, currently there is no approved drug capable of obviating preformed biofilms which increases the chance of infection relapses. Here, we screened a small molecule Prestwick Chemical Library, consisting of 1200 FDA approved off-patent drugs, against C. albicans, C. auris and A. fumigatus, to identify those that inhibit growth of all three pathogens. Inhibitors were further prioritized for their potency against other fungal pathogens, and their ability to kill preformed biofilms. Our studies identified the bis-biguanide Alexidine dihydrochloride (AXD), as a drug with the highest antifungal and anti-biofilm activity against a diverse range of fungal pathogens. Finally, AXD significantly potentiated the efficacy of fluconazole against biofilms, displayed low mammalian cell toxicity, and eradicated biofilms growing in mice central venous catheters in vivo, highlighting its potential as a pan-antifungal drug.ImportanceThe prevalence of fungal infections has seen a rise in the past decades due to advances in modern medicine leading to an expanding population of device-associated and immunocompromised patients. Furthermore, the spectrum of pathogenic fungi has changed, with the emergence of multi-drug resistant strains such as C. auris. High mortality related to fungal infections point to major limitations of current antifungal therapy, and an unmet need for new antifungal drugs. We screened a library of repurposed FDA approved inhibitors to identify compounds with activities against a diverse range of fungi, in varied phases of growth. The assays identified Alexidine dihydrochloride (AXD) to have pronounced antifungal activity including against preformed biofilms, at concentrations lower than mammalian cell toxicity. AXD potentiated the activity of fluconazole and amphotericin B against Candida biofilms in vitro, and prevented biofilm growth in vivo. Thus AXD has the potential to be developed as a pan-antifungal, anti-biofilm drug.

Mammalian cell toxicity and bacterial mutagenicity of nitrosoimidazoles

1988 ◽  
Vol 37 (13) ◽  
pp. 2603-2606 ◽  
Author(s):  
William J. Ehlhardt ◽  
Bernard B. Beaulieu ◽  
Peter Goldman
Keyword(s):  
Mammalian Cell ◽  
Cell Toxicity ◽  
Mammalian Cell Toxicity

scholarly journals Alexidine Dihydrochloride Has Broad-Spectrum Activities against Diverse Fungal Pathogens

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Zeinab Mamouei ◽  
Abdullah Alqarihi ◽  
Shakti Singh ◽  
Shuying Xu ◽  
Michael K. Mansour ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Immunocompromised Patients ◽  
Cell Toxicity ◽  
Diverse Range ◽  
Content Type ◽  
Mammalian Cell Toxicity

ABSTRACT Invasive fungal infections due to Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans constitute a substantial threat to hospitalized immunocompromised patients. Further, the presence of drug-recalcitrant biofilms on medical devices and emergence of drug-resistant fungi, such as Candida auris, introduce treatment challenges with current antifungal drugs. Worse, currently there is no approved drug capable of obviating preformed biofilms, which increase the chance of infection relapses. Here, we screened a small-molecule New Prestwick Chemical Library, consisting of 1,200 FDA-approved off-patent drugs against C. albicans, C. auris, and A. fumigatus, to identify those that inhibit growth of all three pathogens. Inhibitors were further prioritized for their potency against other fungal pathogens and their ability to kill preformed biofilms. Our studies identified the bis-biguanide alexidine dihydrochloride (AXD) as a drug with the highest antifungal and antibiofilm activity against a diverse range of fungal pathogens. Finally, AXD significantly potentiated the efficacy of fluconazole against biofilms, displayed low mammalian cell toxicity, and eradicated biofilms growing in mouse central venous catheters in vivo, highlighting its potential as a pan-antifungal drug. IMPORTANCE The prevalence of fungal infections has seen a rise in the past decades due to advances in modern medicine leading to an expanding population of device-associated and immunocompromised patients. Furthermore, the spectrum of pathogenic fungi has changed, with the emergence of multidrug-resistant strains such as C. auris. High mortality related to fungal infections points to major limitations of current antifungal therapy and an unmet need for new antifungal drugs. We screened a library of repurposed FDA-approved inhibitors to identify compounds with activities against a diverse range of fungi in varied phases of growth. The assays identified alexidine dihydrochloride (AXD) to have pronounced antifungal activity, including against preformed biofilms, at concentrations lower than mammalian cell toxicity. AXD potentiated the activity of fluconazole and amphotericin B against Candida biofilms in vitro and prevented biofilm growth in vivo. Thus, AXD has the potential to be developed as a pan-antifungal, antibiofilm drug.

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