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Authordc.contributor.authorQuaglio, Deborah 
Authordc.contributor.authorMangoni, María Luisa 
Authordc.contributor.authorStefanelli, Roberta 
Authordc.contributor.authorCorradi, Silvia 
Authordc.contributor.authorCasciaro, Bruno 
Authordc.contributor.authorVergine, Valeria 
Authordc.contributor.authorLucantoni, Federica 
Authordc.contributor.authorCavinato, Luca 
Authordc.contributor.authorCammarone, Silvia 
Authordc.contributor.authorLoffredo, María Rosa 
Authordc.contributor.authorCappiello, Floriana 
Authordc.contributor.authorCalcaterra, Andrea 
Authordc.contributor.authorErazo Giuffra, Silvia 
Authordc.contributor.authorGhirga, Francesca 
Authordc.contributor.authorMori, Mattia 
Authordc.contributor.authorImperi, Francesco 
Authordc.contributor.authorAscenzioni, Fiorentina 
Authordc.contributor.authorBotta, Bruno 
Admission datedc.date.accessioned2020-11-24T18:59:01Z
Available datedc.date.available2020-11-24T18:59:01Z
Publication datedc.date.issued2020
Cita de ítemdc.identifier.citationJ. Org. Chem. 2020, 85, 10891−10901es_ES
Identifierdc.identifier.other10.1021/acs.joc.0c01459
Identifierdc.identifier.urihttps://repositorio.uchile.cl/handle/2250/177865
Abstractdc.description.abstractColistin is a last-resort antibiotic for the treatment of multidrug resistant Gram-negative bacterial infections. Recently, a natural ent-beyerene diterpene was identified as a promising inhibitor of the enzyme responsible for colistin resistance mediated by lipid A aminoarabinosylation in Gram-negative bacteria, namely, ArnT (undecaprenyl phosphate-alpha-4-amino-4-deoxy-L-arabinose arabinosyl transferase). Here, semisynthetic analogues of hit were designed, synthetized, and tested against colistin-resistant Pseudomonas aeruginosa strains including clinical isolates to exploit the versatility of the diterpene scaffold. Microbiological assays coupled with molecular modeling indicated that for a more efficient colistin adjuvant activity, likely resulting from inhibition of the ArnT activity by the selected compounds and therefore from their interaction with the catalytic site of ArnT, an ent-beyerane scaffold is required along with an oxalate-like group at C-18/C-19 or a sugar residue at C-19 to resemble L-Ara4N. The ent-beyerane skeleton is identified for the first time as a privileged scaffold for further cost-effective development of valuable colistin resistance inhibitors.es_ES
Patrocinadordc.description.sponsorshipIstituto Pasteur Italia Fondazione Cenci Bolognetti Ministry of Health, Italy Italian Cystic Fibrosis Research Foundation 15/2019 Excellence Departments grant from MIUR commi 314-337 Legge 232/2016 Departments of Chemistry and Technology of Drugs of the Sapienza University of Rome Department of Biotechnology, Chemistry and Pharmacy of the University of Siena PON (Piano Operativo Nazionale) ARS01_00432 03/2018-09/2020 Ministry of Education, Universities and Research (MIUR) Research Projects of National Relevance (PRIN) Sapienza University RM11816436113D8A European Cooperation in Science and Technology (COST) CM1407es_ES
Lenguagedc.language.isoenes_ES
Publisherdc.publisherAmerican Chemical Societyes_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
Sourcedc.sourceJournal of Organic Chemistry (The Journal of Organic Chemistry)es_ES
Títulodc.titleent-Beyerane Diterpenes as a Key Platform for the Development of ArnT-Mediated Colistin Resistance Inhibitorses_ES
Document typedc.typeArtículo de revistaes_ES
dcterms.accessRightsdcterms.accessRightsAcceso Abierto
Catalogueruchile.catalogadorctces_ES
Indexationuchile.indexArtículo de publicación ISI
Indexationuchile.indexArtículo de publicación SCOPUS


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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile