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Pregled bibliografske jedinice broj: 1202311

New membrane active antibacterial andantiviral amphiphiles derived from heterocyclic backbone of pyridinium-4- aldoxime


Crnčević, Doris; Krce, Lucija; Cvitković, Mislav; Brkljača, Zlatko; Sabljić, Antonio; Vuko, Elma; Primožič, Ines; Odžak, Renata; Šprung, Matilda
New membrane active antibacterial andantiviral amphiphiles derived from heterocyclic backbone of pyridinium-4- aldoxime // Pharmaceuticals, 15 (2022), 7; 775, 21 doi:10.3390/ph15070775 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 1202311 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
New membrane active antibacterial andantiviral amphiphiles derived from heterocyclic backbone of pyridinium-4- aldoxime

Autori
Crnčević, Doris ; Krce, Lucija ; Cvitković, Mislav ; Brkljača, Zlatko ; Sabljić, Antonio ; Vuko, Elma ; Primožič, Ines ; Odžak, Renata ; Šprung, Matilda

Izvornik
Pharmaceuticals (1424-8247) 15 (2022), 7; 775, 21

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
quaternary ammonium salts ; pyridinium-4-aldoxime ; antimicrobial activity ; cytotoxicity ; mode of action mechanism

Sažetak
Quaternary ammonium salts (QAS) are irreplaceable membrane- active antimicrobial agents that have been widely used for nearly a century. Cetylpyridinium chloride (CPC) is one of the most potent QAS. However, recent data from the literature indicate that CPC activity against resistant bacterial strains is decreasing. The major QAS resistance pathway involves the QacR dimer, which regulates efflux pump expression. A plausible approach to address this issue is to structurally modify the CPC structure by adding other biologically active functional groups. Here, a series of QAS based on pyridine-4- aldoxime were synthesized, characterized, and tested for antimicrobial activity in vitro. Although we obtained several potent antiviral candidates, these candidates had lower antibacterial activity than CPC and were not toxic to human cell lines. We found that the addition of an oxime group to the pyridine backbone resulted in derivatives with large topological polar surfaces and with unfavorable cLog P values. Investigation of the antibacterial mode of action, involving the cell membrane, revealed altered cell morphologies in terms of corrugated and/or disrupted surface, while 87% of the cells studied exhibited a permeabilized membrane after 3 h of treatment at 4 × minimum inhibitory concentration (MIC). Molecular dynamic (MD) simulations of the interaction of QacR with a representative candidate showed rapid dimer disruption, whereas this was not observed for QacR and QacR bound to the structural analog CPC. This might explain the lower bioactivity of our compounds, as they are likely to cause premature expression of efflux pumps and thus activation of resistance.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekti:
HRZZ-UIP-2020-02-2356 - Otkriće i razvoj novih biološki aktivnih kvaternih amonijevih spojeva derivata kinuklidina (QACBioAct) (Šprung, Matilda, HRZZ ) ( POIROT)

Ustanove:
Institut "Ruđer Bošković", Zagreb,
Prirodoslovno-matematički fakultet, Zagreb,
Prirodoslovno-matematički fakultet, Split

Poveznice na cjeloviti tekst rada:

doi www.mdpi.com

Citiraj ovu publikaciju:

Crnčević, Doris; Krce, Lucija; Cvitković, Mislav; Brkljača, Zlatko; Sabljić, Antonio; Vuko, Elma; Primožič, Ines; Odžak, Renata; Šprung, Matilda
New membrane active antibacterial andantiviral amphiphiles derived from heterocyclic backbone of pyridinium-4- aldoxime // Pharmaceuticals, 15 (2022), 7; 775, 21 doi:10.3390/ph15070775 (međunarodna recenzija, članak, znanstveni)
Crnčević, D., Krce, L., Cvitković, M., Brkljača, Z., Sabljić, A., Vuko, E., Primožič, I., Odžak, R. & Šprung, M. (2022) New membrane active antibacterial andantiviral amphiphiles derived from heterocyclic backbone of pyridinium-4- aldoxime. Pharmaceuticals, 15 (7), 775, 21 doi:10.3390/ph15070775.
@article{article, author = {Crn\v{c}evi\'{c}, Doris and Krce, Lucija and Cvitkovi\'{c}, Mislav and Brklja\v{c}a, Zlatko and Sablji\'{c}, Antonio and Vuko, Elma and Primo\v{z}i\v{c}, Ines and Od\v{z}ak, Renata and \v{S}prung, Matilda}, year = {2022}, pages = {21}, DOI = {10.3390/ph15070775}, chapter = {775}, keywords = {quaternary ammonium salts, pyridinium-4-aldoxime, antimicrobial activity, cytotoxicity, mode of action mechanism}, journal = {Pharmaceuticals}, doi = {10.3390/ph15070775}, volume = {15}, number = {7}, issn = {1424-8247}, title = {New membrane active antibacterial andantiviral amphiphiles derived from heterocyclic backbone of pyridinium-4- aldoxime}, keyword = {quaternary ammonium salts, pyridinium-4-aldoxime, antimicrobial activity, cytotoxicity, mode of action mechanism}, chapternumber = {775} }
@article{article, author = {Crn\v{c}evi\'{c}, Doris and Krce, Lucija and Cvitkovi\'{c}, Mislav and Brklja\v{c}a, Zlatko and Sablji\'{c}, Antonio and Vuko, Elma and Primo\v{z}i\v{c}, Ines and Od\v{z}ak, Renata and \v{S}prung, Matilda}, year = {2022}, pages = {21}, DOI = {10.3390/ph15070775}, chapter = {775}, keywords = {quaternary ammonium salts, pyridinium-4-aldoxime, antimicrobial activity, cytotoxicity, mode of action mechanism}, journal = {Pharmaceuticals}, doi = {10.3390/ph15070775}, volume = {15}, number = {7}, issn = {1424-8247}, title = {New membrane active antibacterial andantiviral amphiphiles derived from heterocyclic backbone of pyridinium-4- aldoxime}, keyword = {quaternary ammonium salts, pyridinium-4-aldoxime, antimicrobial activity, cytotoxicity, mode of action mechanism}, chapternumber = {775} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus


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