Pregled bibliografske jedinice broj: 1213960
New membrane active antimicrobial amphiphiles derived from heterocyclic backbone of pyridinium-4-aldoxime
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
Profili:
Lucija Krce (autor)
Ines Primožič (autor)
Antonio Sabljić (autor)
Mislav Cvitković (autor)
Matilda Šprung (autor)
Renata Odžak (autor)
Doris Crnčević (autor)