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Pregled bibliografske jedinice broj: 1213960

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


Crnčević, Doris; Krce, Lucija; Cvitković, Mislav; Sabljić, Antonio; Primožič, Ines; Odžak, Renata; Šprung, Matilda
New membrane active antimicrobial amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime // International Symposium on Medicinal Chemistry
Nica, Francuska, 2022. (poster, međunarodna recenzija, neobjavljeni rad, znanstveni)


CROSBI ID: 1213960 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

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

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

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
International Symposium on Medicinal Chemistry

Mjesto i datum
Nica, Francuska, 04.09.2022. - 08.09.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Amphiphiles ; quaternary ammonium compounds ; pyridinium-4-aldoxime ; antimicrobial activity

Sažetak
Quaternary ammonium salts (QASs) are irreplaceable membrane- active antimicrobial agents that have been widely used for almost a century. Cetylpyridinium chloride (CPC) is one of the most potent QASs, however, recent data from the literature indicate a 2- to 4-fold decrease in CPC activity against resistant bacterial strains. Given the growing demand for effective antimicrobials, especially in times of current and future spread of infectious diseases, the number of resistant isolates is expected to increase. One plausible approach to address this problem is to structurally modify the CPC structure by adding other biologically active functional groups. Here, a series of QASs based on pyridine-4-aldoxime were synthesized, characterized, and tested for antimicrobial activity in vitro. Although we obtained several potent antiviral candidates, Py- C12Br, Py-C12, and Py-C14, these candidates had lower antibacterial activity than commercial CPC. AFM images showed damage to the cell membrane and no viable cells after the bacteria were exposed to 4xMIC of Py-C12 for 3 hours. We found that the addition of an oxime group to the pyridine backbone resulted in an unfavorable electron density distribution and cLogP values and disrupted the interaction with the QacR dimer that regulates efflux pump expression. MD simulations showed that binding of Py-C16 to QacR leads to dissociation of the dimer within 50 ns, whereas the same was not observed in the case of the QacR dimer and the QacR dimer bound to CPC. This explains the lower bioactivity of our compounds, as they are likely to induce premature expression of the efflux pumps.

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 ) ( CroRIS)

Ustanove:
Prirodoslovno-matematički fakultet, Zagreb,
Prirodoslovno-matematički fakultet, Split


Citiraj ovu publikaciju:

Crnčević, Doris; Krce, Lucija; Cvitković, Mislav; Sabljić, Antonio; Primožič, Ines; Odžak, Renata; Šprung, Matilda
New membrane active antimicrobial amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime // International Symposium on Medicinal Chemistry
Nica, Francuska, 2022. (poster, međunarodna recenzija, neobjavljeni rad, znanstveni)
Crnčević, D., Krce, L., Cvitković, M., Sabljić, A., Primožič, I., Odžak, R. & Šprung, M. (2022) New membrane active antimicrobial amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime. U: International Symposium on Medicinal Chemistry.
@article{article, author = {Crn\v{c}evi\'{c}, Doris and Krce, Lucija and Cvitkovi\'{c}, Mislav and Sablji\'{c}, Antonio and Primo\v{z}i\v{c}, Ines and Od\v{z}ak, Renata and \v{S}prung, Matilda}, year = {2022}, keywords = {Amphiphiles, quaternary ammonium compounds, pyridinium-4-aldoxime, antimicrobial activity}, title = {New membrane active antimicrobial amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime}, keyword = {Amphiphiles, quaternary ammonium compounds, pyridinium-4-aldoxime, antimicrobial activity}, publisherplace = {Nica, Francuska} }
@article{article, author = {Crn\v{c}evi\'{c}, Doris and Krce, Lucija and Cvitkovi\'{c}, Mislav and Sablji\'{c}, Antonio and Primo\v{z}i\v{c}, Ines and Od\v{z}ak, Renata and \v{S}prung, Matilda}, year = {2022}, keywords = {Amphiphiles, quaternary ammonium compounds, pyridinium-4-aldoxime, antimicrobial activity}, title = {New membrane active antimicrobial amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime}, keyword = {Amphiphiles, quaternary ammonium compounds, pyridinium-4-aldoxime, antimicrobial activity}, publisherplace = {Nica, Francuska} }




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