Pregled bibliografske jedinice broj: 1233419
Synthesis and antibacterial activity of 3-aminoquinuclidine quaternary ammonium salts
Synthesis and antibacterial activity of 3-aminoquinuclidine quaternary ammonium salts // The 6th Mini Symposium of Section of Medicinal and Pharmaceutical Chemistry
Zagreb, Hrvatska, 2022. (predavanje, nije recenziran, neobjavljeni rad, znanstveni)
CROSBI ID: 1233419 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Synthesis and antibacterial activity of
3-aminoquinuclidine quaternary ammonium salts
Autori
Sabljić, Antonio ; Crnčević, Doris ; Šprung, Matilda ; Odžak, Renata
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni
Skup
The 6th Mini Symposium of Section of Medicinal and Pharmaceutical Chemistry
Mjesto i datum
Zagreb, Hrvatska, 22.11.2022
Vrsta sudjelovanja
Predavanje
Vrsta recenzije
Nije recenziran
Ključne riječi
soft QACs, 3-aminoquinuclidine, antibacterial activity
Sažetak
Bacterial resistance to available antibiotics is a growing problem in the combat against pathogens that cause various diseases in humans. Since quaternary ammonium compounds (QACs) have a membranolytic effect, they are known for their antibacterial properties. Literature data show that introducing an amide functional group into their structure results in soft QACs with improved antimicrobial properties. By introducing an amide functional group into the structure of QACs provides the possibility of controlled regulation of their biological activity. The aim of this investigation is the de novo synthesis of QACs based on the 3-aminoquinuclidine scaffold with long alkyl chains with amide functionalization connected to the quaternary center by a methylene bridge. Base catalyzed synthesis of the convenient amide with alkyl chains of different lengths (12, 14 and 16 C-atoms) was carried out in dry dichloromethane from 5 °C to room temperature. 3- aminoquinuclidine quaternization reactions were carried out in dry acetonitrile with the appropriate amount of synthesized amide at reflux conditions. For these QACs cLogP values, i.e., lipophilicity coefficients were calculated using the online tool SwissADME. Obtained values indicate that compounds can easily penetrate the bacterial membrane and cause the leakage of cytoplasmic contents and cell lysis. The microbiological activity of the newly synthesized compounds was tested using the microdilution method against a panel of Gram- positive and Gram- negative bacteria. However, the obtained values of minimum inhibitory concentrations (MIC) were higher than expected (≥100 µM). Future steps, currently underway in our laboratory, involve investigation of their spontaneous hydrolysis in basic or acidic conditions which will yield inactive degradation products that do not threaten human health and the environment.
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, Split