N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
Autori
Aleksic, IvanaJeremic, Jelena
Milivojević, Dušan
Ilić-Tomić, Tatjana
Šegan, Sandra B.
Zlatović, Mario
Opsenica, Dejan M.
Senerovic, Lidija
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.
Ključne reči:
Long-Chained 4-Amino-7-chloro-quionolines / Pseudomonas aeruginosa / quorum sensing / Inhibitors of PyocyaninIzvor:
ACS Chemical Biology, 2019Izdavač:
- American Chemical Society
Finansiranje / projekti:
- Sinteza aminohinolina i njihovih derivata kao antimalarika i inhibitora botulinum neurotoksina A (RS-MESTD-Basic Research (BR or ON)-172008)
- Izučavanje mikrobiološkog diverziteta i karakterizacija korisnih sredinskih mikroorganizama (RS-MESTD-Basic Research (BR or ON)-173048)
DOI: 10.1021/acschembio.9b00682
ISSN: 1554-8929
PubMed: 31647218
WoS: 000504806100033
Scopus: 2-s2.0-85074933821
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Aleksic, Ivana AU - Jeremic, Jelena AU - Milivojević, Dušan AU - Ilić-Tomić, Tatjana AU - Šegan, Sandra B. AU - Zlatović, Mario AU - Opsenica, Dejan M. AU - Senerovic, Lidija PY - 2019 UR - https://cherry.chem.bg.ac.rs/handle/123456789/3772 AB - Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies. PB - American Chemical Society T2 - ACS Chemical Biology T1 - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa DO - 10.1021/acschembio.9b00682 ER -
@article{ author = "Aleksic, Ivana and Jeremic, Jelena and Milivojević, Dušan and Ilić-Tomić, Tatjana and Šegan, Sandra B. and Zlatović, Mario and Opsenica, Dejan M. and Senerovic, Lidija", year = "2019", abstract = "Pseudomonas aeruginosa is a leading cause of nosocomial infections that are becoming increasingly difficult to treat due to the occurrence of antibiotic resistant strains. Since P. aeruginosa virulence is controlled through quorum sensing, small molecule treatments inhibiting quorum sensing signaling pathways provide a promising therapeutic option. Consequently, we synthesized a series of N-octaneamino-4-aminoquinoline derivatives to optimize this chemotype’s antivirulence activity against P. aeruginosa via inhibition of pyocyanin production. The most potent derivative, which possesses a benzofuran substituent, provided effective inhibition of pyocyanin production (IC50 = 12 μM), biofilm formation (BFIC50 = 50 μM), and motility. Experimentally, the compound’s activity is achieved through competitive inhibition of PqsR, and structure–activity data were rationalized using molecular docking studies.", publisher = "American Chemical Society", journal = "ACS Chemical Biology", title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa", doi = "10.1021/acschembio.9b00682" }
Aleksic, I., Jeremic, J., Milivojević, D., Ilić-Tomić, T., Šegan, S. B., Zlatović, M., Opsenica, D. M.,& Senerovic, L.. (2019). N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology American Chemical Society.. https://doi.org/10.1021/acschembio.9b00682
Aleksic I, Jeremic J, Milivojević D, Ilić-Tomić T, Šegan SB, Zlatović M, Opsenica DM, Senerovic L. N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa. in ACS Chemical Biology. 2019;. doi:10.1021/acschembio.9b00682 .
Aleksic, Ivana, Jeremic, Jelena, Milivojević, Dušan, Ilić-Tomić, Tatjana, Šegan, Sandra B., Zlatović, Mario, Opsenica, Dejan M., Senerovic, Lidija, "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa" in ACS Chemical Biology (2019), https://doi.org/10.1021/acschembio.9b00682 . .