Publication:
Repurposing clinically approved cephalosporins for tuberculosis therapy

Simple item page
dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: Biomedical Imaging and Instrumentation Groupes
dc.contributor.authorRamón García, Santiago
dc.contributor.authorGonzález Del Río, Rubén
dc.contributor.authorSantos Villarejo, Ángel
dc.contributor.authorD. Sweet, Gaye
dc.contributor.authorCunningham, Fraser
dc.contributor.authorBarros, David
dc.contributor.authorBallell, Lluis
dc.contributor.authorMendoza Losana, Alfonso
dc.contributor.authorFerrer Bazaga, Santiago
dc.contributor.authorJ. Thompson, Charles
dc.contributor.funderEuropean Commissionen
dc.date.accessioned2023-11-15T15:07:36Z
dc.date.available2023-11-15T15:07:36Z
dc.date.issued2016-09-28
dc.description.abstractWhile modern cephalosporins developed for broad spectrum antibacterial activities have never been pursued for tuberculosis (TB) therapy, we identified first generation cephalosporins having clinically relevant inhibitory concentrations, both alone and in synergistic drug combinations. Common chemical patterns required for activity against Mycobacterium tuberculosis were identified using structure-activity relationships (SAR) studies. Numerous cephalosporins were synergistic with rifampicin, the cornerstone drug for TB therapy and ethambutol, a first-line anti-TB drug. Synergy was observed even under intracellular growth conditions where beta-lactams typically have limited activities. Cephalosporins and rifampicin were 4- to 64-fold more active in combination than either drug alone; however, limited synergy was observed with rifapentine or rifabutin. Clavulanate was a key synergistic partner in triple combinations. Cephalosporins (and other beta-lactams) together with clavulanate rescued the activity of rifampicin against a rifampicin resistant strain. Synergy was not due exclusively to increased rifampicin accumulation within the mycobacterial cells. Cephalosporins were also synergistic with new anti-TB drugs such as bedaquiline and delamanid. Studies will be needed to validate their in vivo activities. However, the fact that cephalosporins are orally bioavailable with good safety profiles, together with their anti-mycobacterial activities reported here, suggest that they could be repurposed within new combinatorial TB therapies.en
dc.description.sponsorshipThis work was supported by grants from the British Columbia Lung Association and The Canadian Institute of Health Research (MOP-82855) to C.J.T. and from a Grand Challenges Canada - Stars in Global Health (0030-01-04-01-01) and a People Programme (Marie Skłodowska Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA agreement no. 291799 (Tres Cantos Open Lab Foundation - COFUND programme) to S.R.-G.en
dc.identifier.bibliographicCitationRamón-García, S., González del Río, R., Villarejo, A. S., Sweet, G. D., Cunningham, F., Barros, D., Ballell, L., Mendoza-Losana, A., Ferrer-Bazaga, S., & Thompson, C. J. (2016). Repurposing clinically approved cephalosporins for tuberculosis therapy. Scientific Reports, 6 (1).es
dc.identifier.doihttps://doi.org/10.1038/srep34293
dc.identifier.issn2045-2322
dc.identifier.publicationissue34293es
dc.identifier.publicationtitleScientific Reportsen
dc.identifier.publicationvolume6es
dc.identifier.urihttps://hdl.handle.net/10016/38872
dc.identifier.uxxiAR/0000030687
dc.language.isoenges
dc.publisherSpringeres
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/291799es
dc.rights© The authorses
dc.rightsAtribución 3.0 España*
dc.rights.accessRightsopen accesses
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subject.ecienciaMedicinaes
dc.titleRepurposing clinically approved cephalosporins for tuberculosis therapyen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
repurposing_SR_2016.pdf
Size:
1.76 MB
Format:
Adobe Portable Document Format
Download
Collections
DBIAB - BIIG - Journal Articles