KFU. Card publication. Targeting pathogenic fungi, bacteria and fungal-bacterial biofilms by newly synthesized quaternary ammonium derivative of pyridoxine and terbinafine with dual action profile

- RUS
- 中文
- ES

TARGETING PATHOGENIC FUNGI, BACTERIA AND FUNGAL-BACTERIAL BIOFILMS BY NEWLY SYNTHESIZED QUATERNARY AMMONIUM DERIVATIVE OF PYRIDOXINE AND TERBINAFINE WITH DUAL ACTION PROFILE

Form of presentation

Articles in international journals and collections

Year of publication

2020

��

��

Authors, employees of KFU

Bogachev Mikhail Igorevich, author

Kayumov Ayrat Rashitovich, author

Laykov Aleksandr Vladimirovich, author

Pavelev Roman Sergeevich, author

Bibliographic description in the original language

Garipov M.R, Sabirova A.E, Pavelyev R.S, Targeting pathogenic fungi, bacteria and fungal-bacterial biofilms by newly synthesized quaternary ammonium derivative of pyridoxine and terbinafine with dual action profile//Bioorganic Chemistry. - 2020. - Vol.104, Is.. - Art. � 104306.

Annotation

Many pathogenic bacteria and microscopic fungi form rigid polymicrobial biofilms this way enhancing their resistant to treatment. A series of novel pyridoxine-based quaternary ammonium derivatives of terbinafine characterized by both antifungal and antibacterial activities was designed. The leading compound named KFU-127 exhibits promising antifungal and antibacterial activities against various bacteria and micromycetes in both planktonic and biofilm-embedded forms demonstrating MIC values comparable with those of conventional antifungals and antimicrobials. Similar to other antiseptics like benzalkonium chloride and miramistin, KFU-127 is considerably toxic for eukaryotic cells that limits is application to topical treatment options. On the other hand, KFU-127 reduces the number of viable biofilm-embedded bacteria and C. albicans by 3 orders of magnitude at concentrations 2–4 times lower than those of reference drugs and successfully eradicates S. aureus-C. albicans mixed biofilms. The mechanism of antimicrobial action of KFU-127 is bimodal including both membrane integrity damage and pyridoxal-dependent enzymes targeting. We expect that this bilateral mechanism would result in lower rates of resistance development in both fungal and bacterial pathogens. Taken together, our data suggest KFU-127 as a new promising broad spectrum topical antimicrobial capable of one-shot targeting of bacterial and fungal-bacterial biofilms.

Keywords

Antifungals Antimicrobials Quaternary ammonium compounds (QAC) Terbinafine Pyridoxine Biofilms

The name of the journal

Bioorganic Chemistry

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091800881&doi=10.1016%2fj.bioorg.2020.104306&partnerID=40&md5=5d45a12b6fa0e7db459d297ae4da4557

Please use this ID to quote from or refer to the card

https://repository.kpfu.ru/eng/?p_id=240205&p_lang=2

Full metadata record

Field DC	Value	Language
dc.contributor.author	Bogachev Mikhail Igorevich	ru_RU
dc.contributor.author	Kayumov Ayrat Rashitovich	ru_RU
dc.contributor.author	Laykov Aleksandr Vladimirovich	ru_RU
dc.contributor.author	Pavelev Roman Sergeevich	ru_RU
dc.date.accessioned	2020-01-01T00:00:00Z	ru_RU
dc.date.available	2020-01-01T00:00:00Z	ru_RU
dc.date.issued	2020	ru_RU
dc.identifier.citation	Garipov M.R, Sabirova A.E, Pavelyev R.S, Targeting pathogenic fungi, bacteria and fungal-bacterial biofilms by newly synthesized quaternary ammonium derivative of pyridoxine and terbinafine with dual action profile//Bioorganic Chemistry. - 2020. - Vol.104, Is.. - Art. � 104306.	ru_RU
dc.identifier.uri	https://repository.kpfu.ru/eng/?p_id=240205&p_lang=2	ru_RU
dc.description.abstract	Bioorganic Chemistry	ru_RU
dc.description.abstract	Many pathogenic bacteria and microscopic fungi form rigid polymicrobial biofilms this way enhancing their resistant to treatment. A series of novel pyridoxine-based quaternary ammonium derivatives of terbinafine characterized by both antifungal and antibacterial activities was designed. The leading compound named KFU-127 exhibits promising antifungal and antibacterial activities against various bacteria and micromycetes in both planktonic and biofilm-embedded forms demonstrating MIC values comparable with those of conventional antifungals and antimicrobials. Similar to other antiseptics like benzalkonium chloride and miramistin, KFU-127 is considerably toxic for eukaryotic cells that limits is application to topical treatment options. On the other hand, KFU-127 reduces the number of viable biofilm-embedded bacteria and C. albicans by 3 orders of magnitude at concentrations 2–4 times lower than those of reference drugs and successfully eradicates S. aureus-C. albicans mixed biofilms. The mechanism of antimicrobial action of KFU-127 is bimodal including both membrane integrity damage and pyridoxal-dependent enzymes targeting. We expect that this bilateral mechanism would result in lower rates of resistance development in both fungal and bacterial pathogens. Taken together, our data suggest KFU-127 as a new promising broad spectrum topical antimicrobial capable of one-shot targeting of bacterial and fungal-bacterial biofilms.	ru_RU
dc.language.iso	ru	ru_RU
dc.subject		ru_RU
dc.title	Targeting pathogenic fungi, bacteria and fungal-bacterial biofilms by newly synthesized quaternary ammonium derivative of pyridoxine and terbinafine with dual action profile	ru_RU
dc.type	Articles in international journals and collections	ru_RU