N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa
Authors
Aleksic, IvanaJeremić, Jelena
Milivojevic, Dusan
Ilić-Tomić, Tatjana

Šegan, Sandra

Zlatović, Mario

Opsenica, Dejan

Senerovic, Lidija

Article (Accepted 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 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.
Keywords:
Long-Chained 4-Amino-7-chloro-quionolines / Pseudomonas aeruginosa / quorum sensing / Inhibitors of PyocyaninSource:
ACS Chemical Biology, 2019, 14, 12, 2800-2809Publisher:
- American Chemical Society (ACS)
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-173048)
Note:
- This is the peer-reviewed version of the article: Ivana Aleksic, Jelena Jeremic, Dusan Milivojevic, Tatjana Ilic-Tomic, Sandra Šegan, Mario Zlatović, Dejan M. Opsenica, Lidija Senerovic, ACS Chem. Biol. 2019, 14, 12, 2800-2809, https://doi.org/10.1021/acschembio.9b00682
- The published version: http://cer.ihtm.bg.ac.rs/handle/123456789/3198
DOI: 10.1021/acschembio.9b00682
ISSN: 1554-8929
PubMed: 31647218
WoS: 000504806100033
Scopus: 2-s2.0-85074933821
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IHTMTY - JOUR AU - Aleksic, Ivana AU - Jeremić, Jelena AU - Milivojevic, Dusan AU - Ilić-Tomić, Tatjana AU - Šegan, Sandra AU - Zlatović, Mario AU - Opsenica, Dejan AU - Senerovic, Lidija PY - 2019 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/3198 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/3341 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 (ACS) T2 - ACS Chemical Biology T1 - N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa VL - 14 IS - 12 SP - 2800 EP - 2809 DO - 10.1021/acschembio.9b00682 ER -
@article{ author = "Aleksic, Ivana and Jeremić, Jelena and Milivojevic, Dusan and Ilić-Tomić, Tatjana and Šegan, Sandra and Zlatović, Mario and Opsenica, Dejan 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 (ACS)", journal = "ACS Chemical Biology", title = "N-benzyl derivatives of long-chained 4-Amino-7-chloro-quionolines as inhibitors of pyocyanin production in Pseudomonas aeruginosa", volume = "14", number = "12", pages = "2800-2809", doi = "10.1021/acschembio.9b00682" }
Aleksic, I., Jeremić, J., Milivojevic, D., Ilić-Tomić, T., Šegan, S., Zlatović, M., Opsenica, D.,& 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 (ACS)., 14(12), 2800-2809. https://doi.org/10.1021/acschembio.9b00682
Aleksic I, Jeremić J, Milivojevic D, Ilić-Tomić T, Šegan S, Zlatović M, Opsenica D, 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;14(12):2800-2809. doi:10.1021/acschembio.9b00682 .
Aleksic, Ivana, Jeremić, Jelena, Milivojevic, Dusan, Ilić-Tomić, Tatjana, Šegan, Sandra, Zlatović, Mario, Opsenica, Dejan, 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, 14, no. 12 (2019):2800-2809, https://doi.org/10.1021/acschembio.9b00682 . .