Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa
Authors
Aleksić, Ivana
Šegan, Sandra

Andrić, Filip

Zlatović, Mario

Moric, Ivana
Opsenica, Dejan

Senerovic, Lidija

Article (Accepted Version)
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Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topol...ogical charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.
Source:
Acs Chemical Biology, 2017, 12, 5, 1425-1434Publisher:
- American Chemical Society (ACS)
Funding / projects:
- Microbial diversity study and characterization of beneficial environmental microorganisms (RS-173048)
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Note:
- This is the peer-reviewed version of the following article: Aleksić, I.; Šegan, S.; Andrić, F.; Zlatović, M.; Moric, I.; Opsenica, D. M.; Senerovic, L. Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia Marcescens and Pseudomonas Aeruginosa. ACS Chemical Biology 2017, 12 (5), 1425–1434, https://doi.org/10.1021/acschembio.6b01149
- http://cer.ihtm.bg.ac.rs/handle/123456789/2270
DOI: 10.1021/acschembio.6b01149
ISSN: 1554-8929
WoS: 000402023300029
Scopus: 2-s2.0-85019737266
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IHTMTY - JOUR AU - Aleksić, Ivana AU - Šegan, Sandra AU - Andrić, Filip AU - Zlatović, Mario AU - Moric, Ivana AU - Opsenica, Dejan AU - Senerovic, Lidija PY - 2017 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2983 AB - Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species. PB - American Chemical Society (ACS) T2 - Acs Chemical Biology T1 - Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa VL - 12 IS - 5 SP - 1425 EP - 1434 DO - 10.1021/acschembio.6b01149 ER -
@article{ author = "Aleksić, Ivana and Šegan, Sandra and Andrić, Filip and Zlatović, Mario and Moric, Ivana and Opsenica, Dejan and Senerovic, Lidija", year = "2017", abstract = "Antibiotic resistance has become a serious global threat to public health; therefore, improved strategies and structurally novel antimicrobials are urgently needed to combat infectious diseases. Here we report a new type of highly potent 4-aminoquinoline derivatives as quorum sensing inhibitors in Serratia marcescens and Pseudomonas aeruginosa, exhibiting weak bactericidal activities (minimum inhibitory concentration (MIC) > 400 mu M). Through detailed structure-activity study, we have identified 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines (5 and 10) as biofilm formation inhibitors with 50% biofilm inhibition at 69 mu M and 63 mu M in S. marcescens and P. aeruginosa, respectively. These two compounds, 5 and 10, are the first quinoline derivatives with anti-biofilm formation activity reported in S. marcescens. Quantitative structure-activity relationship (QSAR) analysis identified structural descriptors such as Wiener indices, hyper-distance-path index (HDPI), mean topological charge (MTC), topological charge index (TCI), and log D(o/w)exp as the most influential in biofilm inhibition in this bacterial species. Derivative 10 is one of the most potent quinoline type inhibitors of pyocyanin production described so far (IC50 = 2.5 mu M). While we have demonstrated that 5 and 10 act as Pseudomonas quinolone system (PQS) antagonists, the mechanism of inhibition of S. marcescens biofilm formation with these compounds remains open since signaling similar to P. aeruginosa PQS system has not yet been described in Serratia and activity of these compounds on acylhomoserine lactone (AHL) signaling has not been detected. Our data show that 7-Cl and 7-CF3 substituted N-dodecylamino-4-aminoquinolines present the promising scaffolds for developing antivirulence and anti-biofilm formation agents against multidrug-resistant bacterial species.", publisher = "American Chemical Society (ACS)", journal = "Acs Chemical Biology", title = "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa", volume = "12", number = "5", pages = "1425-1434", doi = "10.1021/acschembio.6b01149" }
Aleksić, I., Šegan, S., Andrić, F., Zlatović, M., Moric, I., Opsenica, D.,& Senerovic, L.. (2017). Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology American Chemical Society (ACS)., 12(5), 1425-1434. https://doi.org/10.1021/acschembio.6b01149
Aleksić I, Šegan S, Andrić F, Zlatović M, Moric I, Opsenica D, Senerovic L. Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa. in Acs Chemical Biology. 2017;12(5):1425-1434. doi:10.1021/acschembio.6b01149 .
Aleksić, Ivana, Šegan, Sandra, Andrić, Filip, Zlatović, Mario, Moric, Ivana, Opsenica, Dejan, Senerovic, Lidija, "Long-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosa" in Acs Chemical Biology, 12, no. 5 (2017):1425-1434, https://doi.org/10.1021/acschembio.6b01149 . .