Show simple item record

dc.creatorAleksić, Ivana
dc.creatorŠegan, Sandra
dc.creatorAndrić, Filip
dc.creatorZlatović, Mario
dc.creatorMoric, Ivana
dc.creatorOpsenica, Dejan
dc.creatorSenerovic, Lidija
dc.date.accessioned2019-01-30T17:56:55Z
dc.date.available2019-01-30T17:56:55Z
dc.date.issued2017
dc.identifier.issn1554-8929
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/2270
dc.description.abstractAntibiotic 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.en
dc.publisherAmerican Chemical Society (ACS)
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173048/RS//
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.relationEuropean Society of Clinical Microbiology and Infectious Diseases (ESCMID)
dc.rightsrestrictedAccess
dc.sourceAcs Chemical Biology
dc.titleLong-Chain 4-Aminoquinolines as Quorum Sensing Inhibitors in Serratia marcescens and Pseudomonas aeruginosaen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractAндриц, Филип; Опсеница, Дејан; Шеган, Сандра; Aлексић, Ивана; Мориц, Ивана; Златовиц, Марио; Сенеровиц, Лидија;
dc.citation.volume12
dc.citation.issue5
dc.citation.spage1425
dc.citation.epage1434
dc.citation.other12(5): 1425-1434
dc.citation.rankM21
dc.description.otherPeer-reviewed version: [http://cer.ihtm.bg.ac.rs/handle/123456789/2983]
dc.identifier.pmid28350449
dc.identifier.doi10.1021/acschembio.6b01149
dc.identifier.rcubConv_3727
dc.identifier.scopus2-s2.0-85019737266
dc.identifier.wos000402023300029
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record