Copper(II) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa
Само за регистроване кориснике
2016
Аутори
Glišić, Biljana Đ.Aleksić, Ivana
Comba, Peter
Wadepohl, Hubert
Ilić-Tomić, Tatjana
Nikodinović-Runić, Jasmina
Đuran, Miloš I.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Five copper(II) complexes 1-5 with aromatic nitrogen-containing heterocycles, pyrimidine (pm, 1), pyrazine (pz, 2), quinazoline (qz, 3 and 4) and phthalazine (phtz, 5) have been synthesized and structurally characterized by spectroscopic and single-crystal X-ray diffraction techniques. The crystallographic results show that, dependent on the ligand structure, complexes 1-5 are of different nuclearity. The antimicrobial efficiency of complexes 1-5 has been evaluated against three clinically relevant microorganisms and none of the complexes showed significant growth inhibiting activity, with values of minimum inhibitory concentrations (MIC) in the mM range. Since in many bacteria, pathogenicity and virulence are regulated by intercellular communication processes, quorum sensing (QS), the effect of the copper(II) complexes on bacterial QS has also been examined. The results indicate that the investigated complexes inhibit violacein production in Chromobacterium violaceum CV026, suggesting... an anti-QS activity. In order to differentiate, which of the QS pathways was affected by the copper(II) complexes, three biosensor strains were used: the PAO1 Delta rhlIpKD-rhlA and the PA14-R3 Delta lasIPrsaI lux strain to directly measure the levels of C4-HSL (N-butanoyl-homoserine lactone) and 3OC12-HSL (N-3-oxo-dodecanoyl- homoserine lactone), respectively, and PAO1 Delta pqsA mini-CTX luxPpqsA for the detection of AHQs (2-alkyl-4-quinolones). Complexes 1-5 were shown to be efficient inhibitors of biofilm formation of the human opportunistic pathogen Pseudomonas aeruginosa PAO1, with the qz-containing complex 3 being the most active. Finally, the most anti-QS-active complexes 1 and 3 showed synergistic activity against a multi-drug resistant clinical isolate of P. aeruginosa, when supplied in combination with the known antibiotics piperacillin and ceftazidime.
Кључне речи:
gram-negative bacteria / crystal-structure / chromobacterium-violaceum / biological-activity / spectroscopic properties / biofilm formation / virulence / resistance / strategies / ligandsИзвор:
RSC Advances, 2016, 6, 89, 86695-86709Издавач:
- Royal Soc Chemistry, Cambridge
Финансирање / пројекти:
- Синтеза нових комплекса метала и испитивање њихових реакција са пептидима (RS-MESTD-Basic Research (BR or ON)-172036)
- Изучавање микробиолошког диверзитета и карактеризација корисних срединских микроорганизама (RS-MESTD-Basic Research (BR or ON)-173048)
DOI: 10.1039/c6ra19902j
ISSN: 2046-2069
WoS: 000384322700119
Scopus: 2-s2.0-84987899360
Колекције
Институција/група
Inovacioni centar / Innovation CentreTY - JOUR AU - Glišić, Biljana Đ. AU - Aleksić, Ivana AU - Comba, Peter AU - Wadepohl, Hubert AU - Ilić-Tomić, Tatjana AU - Nikodinović-Runić, Jasmina AU - Đuran, Miloš I. PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2317 AB - Five copper(II) complexes 1-5 with aromatic nitrogen-containing heterocycles, pyrimidine (pm, 1), pyrazine (pz, 2), quinazoline (qz, 3 and 4) and phthalazine (phtz, 5) have been synthesized and structurally characterized by spectroscopic and single-crystal X-ray diffraction techniques. The crystallographic results show that, dependent on the ligand structure, complexes 1-5 are of different nuclearity. The antimicrobial efficiency of complexes 1-5 has been evaluated against three clinically relevant microorganisms and none of the complexes showed significant growth inhibiting activity, with values of minimum inhibitory concentrations (MIC) in the mM range. Since in many bacteria, pathogenicity and virulence are regulated by intercellular communication processes, quorum sensing (QS), the effect of the copper(II) complexes on bacterial QS has also been examined. The results indicate that the investigated complexes inhibit violacein production in Chromobacterium violaceum CV026, suggesting an anti-QS activity. In order to differentiate, which of the QS pathways was affected by the copper(II) complexes, three biosensor strains were used: the PAO1 Delta rhlIpKD-rhlA and the PA14-R3 Delta lasIPrsaI lux strain to directly measure the levels of C4-HSL (N-butanoyl-homoserine lactone) and 3OC12-HSL (N-3-oxo-dodecanoyl- homoserine lactone), respectively, and PAO1 Delta pqsA mini-CTX luxPpqsA for the detection of AHQs (2-alkyl-4-quinolones). Complexes 1-5 were shown to be efficient inhibitors of biofilm formation of the human opportunistic pathogen Pseudomonas aeruginosa PAO1, with the qz-containing complex 3 being the most active. Finally, the most anti-QS-active complexes 1 and 3 showed synergistic activity against a multi-drug resistant clinical isolate of P. aeruginosa, when supplied in combination with the known antibiotics piperacillin and ceftazidime. PB - Royal Soc Chemistry, Cambridge T2 - RSC Advances T1 - Copper(II) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa VL - 6 IS - 89 SP - 86695 EP - 86709 DO - 10.1039/c6ra19902j ER -
@article{ author = "Glišić, Biljana Đ. and Aleksić, Ivana and Comba, Peter and Wadepohl, Hubert and Ilić-Tomić, Tatjana and Nikodinović-Runić, Jasmina and Đuran, Miloš I.", year = "2016", abstract = "Five copper(II) complexes 1-5 with aromatic nitrogen-containing heterocycles, pyrimidine (pm, 1), pyrazine (pz, 2), quinazoline (qz, 3 and 4) and phthalazine (phtz, 5) have been synthesized and structurally characterized by spectroscopic and single-crystal X-ray diffraction techniques. The crystallographic results show that, dependent on the ligand structure, complexes 1-5 are of different nuclearity. The antimicrobial efficiency of complexes 1-5 has been evaluated against three clinically relevant microorganisms and none of the complexes showed significant growth inhibiting activity, with values of minimum inhibitory concentrations (MIC) in the mM range. Since in many bacteria, pathogenicity and virulence are regulated by intercellular communication processes, quorum sensing (QS), the effect of the copper(II) complexes on bacterial QS has also been examined. The results indicate that the investigated complexes inhibit violacein production in Chromobacterium violaceum CV026, suggesting an anti-QS activity. In order to differentiate, which of the QS pathways was affected by the copper(II) complexes, three biosensor strains were used: the PAO1 Delta rhlIpKD-rhlA and the PA14-R3 Delta lasIPrsaI lux strain to directly measure the levels of C4-HSL (N-butanoyl-homoserine lactone) and 3OC12-HSL (N-3-oxo-dodecanoyl- homoserine lactone), respectively, and PAO1 Delta pqsA mini-CTX luxPpqsA for the detection of AHQs (2-alkyl-4-quinolones). Complexes 1-5 were shown to be efficient inhibitors of biofilm formation of the human opportunistic pathogen Pseudomonas aeruginosa PAO1, with the qz-containing complex 3 being the most active. Finally, the most anti-QS-active complexes 1 and 3 showed synergistic activity against a multi-drug resistant clinical isolate of P. aeruginosa, when supplied in combination with the known antibiotics piperacillin and ceftazidime.", publisher = "Royal Soc Chemistry, Cambridge", journal = "RSC Advances", title = "Copper(II) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa", volume = "6", number = "89", pages = "86695-86709", doi = "10.1039/c6ra19902j" }
Glišić, B. Đ., Aleksić, I., Comba, P., Wadepohl, H., Ilić-Tomić, T., Nikodinović-Runić, J.,& Đuran, M. I.. (2016). Copper(II) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa. in RSC Advances Royal Soc Chemistry, Cambridge., 6(89), 86695-86709. https://doi.org/10.1039/c6ra19902j
Glišić BĐ, Aleksić I, Comba P, Wadepohl H, Ilić-Tomić T, Nikodinović-Runić J, Đuran MI. Copper(II) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa. in RSC Advances. 2016;6(89):86695-86709. doi:10.1039/c6ra19902j .
Glišić, Biljana Đ., Aleksić, Ivana, Comba, Peter, Wadepohl, Hubert, Ilić-Tomić, Tatjana, Nikodinović-Runić, Jasmina, Đuran, Miloš I., "Copper(II) complexes with aromatic nitrogen-containing heterocycles as effective inhibitors of quorum sensing activity in Pseudomonas aeruginosa" in RSC Advances, 6, no. 89 (2016):86695-86709, https://doi.org/10.1039/c6ra19902j . .