N-Benzyl Derivatives of Long-Chained 4-Amino-7-chloro-quionolines as Inhibitors of Pyocyanin Production in Pseudomonas aeruginosa
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2019
Authors
Aleksić, IvanaJeremić, Jelena
Milivojević, Dušan
Ilić-Tomić, Tatjana
Segan, Sandra
Zlatović, Mario
Opsenica, Dejan M.
Šenerović, Lidija
Article (Published version)
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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 mu M), biofilm formation (BFIC50 = 50 mu M), and motility. Experimentally, the compound's activity is achieved through competitive inhibition of PqsR, and structure-activity data were rationalized using molecular docking studies.
Source:
Acs Chemical Biology, 2019, 14, 12, 2800-2809Publisher:
- Amer Chemical Soc, Washington
Funding / projects:
- International Centre for Genetic Engineering and Biotechnology, Italy [CRP16-02]
- Reinforcement of the Faculty of Chemistry, University of Belgrade, towards becoming a Center of Excellence in the region of WB for Molecular Biotechnology and Food research (EU-FP7-256716)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-MESTD-Basic Research (BR or ON)-173048)
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-MESTD-Basic Research (BR or ON)-172008)
DOI: 10.1021/acschembio.9b00682
ISSN: 1554-8929
PubMed: 31647218
WoS: 000504806100033
Scopus: 2-s2.0-85074933821
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Aleksić, Ivana AU - Jeremić, Jelena AU - Milivojević, Dušan AU - Ilić-Tomić, Tatjana AU - Segan, Sandra AU - Zlatović, Mario AU - Opsenica, Dejan M. AU - Šenerović, Lidija PY - 2019 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1225 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 mu M), biofilm formation (BFIC50 = 50 mu M), 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 - Amer Chemical Soc, Washington T2 - Acs Chemical Biology T1 - N-Benzyl Derivatives of Long-Chained 4-Amino-7-chloro-quionolines as Inhibitors of Pyocyanin Production in Pseudomonas aeruginosa EP - 2809 IS - 12 SP - 2800 VL - 14 DO - 10.1021/acschembio.9b00682 ER -
@article{ author = "Aleksić, Ivana and Jeremić, Jelena and Milivojević, Dušan and Ilić-Tomić, Tatjana and Segan, Sandra and Zlatović, Mario and Opsenica, Dejan M. and Šenerović, 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 mu M), biofilm formation (BFIC50 = 50 mu M), 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 = "Amer Chemical Soc, Washington", journal = "Acs Chemical Biology", title = "N-Benzyl Derivatives of Long-Chained 4-Amino-7-chloro-quionolines as Inhibitors of Pyocyanin Production in Pseudomonas aeruginosa", pages = "2809-2800", number = "12", volume = "14", doi = "10.1021/acschembio.9b00682" }
Aleksić, I., Jeremić, J., Milivojević, D., Ilić-Tomić, T., Segan, S., Zlatović, M., Opsenica, D. M.,& Šenerović, 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 Amer Chemical Soc, Washington., 14(12), 2800-2809. https://doi.org/10.1021/acschembio.9b00682
Aleksić I, Jeremić J, Milivojević D, Ilić-Tomić T, Segan S, Zlatović M, Opsenica DM, Šenerović 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;14(12):2800-2809. doi:10.1021/acschembio.9b00682 .
Aleksić, Ivana, Jeremić, Jelena, Milivojević, Dušan, Ilić-Tomić, Tatjana, Segan, Sandra, Zlatović, Mario, Opsenica, Dejan M., Šenerović, Lidija, "N-Benzyl Derivatives of Long-Chained 4-Amino-7-chloro-quionolines as Inhibitors of Pyocyanin Production in Pseudomonas aeruginosa" in Acs Chemical Biology, 14, no. 12 (2019):2800-2809, https://doi.org/10.1021/acschembio.9b00682 . .