000065315 001__ 65315
000065315 005__ 20201130083155.0
000065315 0247_ $$2doi$$a10.1080/14756366.2017.1411910
000065315 0248_ $$2sideral$$a104230
000065315 037__ $$aART-2018-104230
000065315 041__ $$aeng
000065315 100__ $$0(orcid)0000-0001-7202-4587$$aSebastián, M.$$uUniversidad de Zaragoza
000065315 245__ $$aDiscovery of antimicrobial compounds targeting bacterial type FAD synthetases
000065315 260__ $$c2018
000065315 5060_ $$aAccess copy available to the general public$$fUnrestricted
000065315 5203_ $$aThe increase of bacterial strains resistant to most of the available antibiotics shows a need to explore novel antibacterial targets to discover antimicrobial drugs. Bifunctional bacterial FAD synthetases (FADSs) synthesise the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors act in vital processes as part of flavoproteins, making FADS an essential enzyme. Bacterial FADSs are potential antibacterial targets because of differences to mammalian enzymes, particularly at the FAD producing site. We have optimised an activity-based high throughput screening assay targeting Corynebacterium ammoniagenes FADS (CaFADS) that identifies inhibitors of its different activities. We selected the three best high-performing inhibitors of the FMN:adenylyltransferase activity (FMNAT) and studied their inhibition mechanisms and binding properties. The specificity of the CaFADS hits was evaluated by studying also their effect on the Streptococcus pneumoniae FADS activities, envisaging differences that can be used to discover species-specific antibacterial drugs. The antimicrobial effect of these compounds was also evaluated on C. ammoniagenes, S. pneumoniae, and Mycobacterium tuberculosis cultures, finding hits with favourable antimicrobial properties.
000065315 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B18$$9info:eu-repo/grantAgreement/ES/MINECO/BIO2016-75183-P
000065315 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000065315 590__ $$a4.027$$b2018
000065315 591__ $$aCHEMISTRY, MEDICINAL$$b9 / 61 = 0.148$$c2018$$dQ1$$eT1
000065315 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b82 / 294 = 0.279$$c2018$$dQ2$$eT1
000065315 592__ $$a0.781$$b2018
000065315 593__ $$aDrug Discovery$$c2018$$dQ2
000065315 593__ $$aPharmacology$$c2018$$dQ2
000065315 593__ $$aMedicine (miscellaneous)$$c2018$$dQ2
000065315 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000065315 700__ $$0(orcid)0000-0002-6649-9153$$aAnoz-Carbonell, E.$$uUniversidad de Zaragoza
000065315 700__ $$aGracia, B.$$uUniversidad de Zaragoza
000065315 700__ $$aCossio, P.
000065315 700__ $$aAínsa, J.A.
000065315 700__ $$aLans, I.
000065315 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, M.$$uUniversidad de Zaragoza
000065315 7102_ $$11008$$2X$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cProy. investigación HQA
000065315 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000065315 773__ $$g33, 1 (2018), 241-254$$pJ. Enzym. Inhib. Med. Chem.$$tJournal of Enzyme Inhibition and Medicinal Chemistry$$x1475-6366
000065315 8564_ $$s1883607$$uhttps://zaguan.unizar.es/record/65315/files/texto_completo.pdf$$yVersión publicada
000065315 8564_ $$s113859$$uhttps://zaguan.unizar.es/record/65315/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000065315 909CO $$ooai:zaguan.unizar.es:65315$$particulos$$pdriver
000065315 951__ $$a2020-11-30-07:57:18
000065315 980__ $$aARTICLE