Blanco-Cabra, NuriaVega-Granados, KarinaMoya-Anderico, LauraVukomanovic, MarijaParra, AndresAlvarez de Cienfuegos, LuisTorrents, Eduard2023-01-252023-01-252019-07-03Blanco-Cabra N, Vega-Granados K, Moya-Andérico L, Vukomanovic M, Parra A, Álvarez de Cienfuegos L, et al. Novel Oleanolic and Maslinic Acid Derivatives as a Promising Treatment against Bacterial Biofilm in Nosocomial Infections: An in Vitro and in Vivo Study. ACS Infect Dis. 2019 Sep 13;5(9):1581-1589.http://hdl.handle.net/10668/14213Oleanolic acid (OA) and maslinic acid (MA) are pentacyclic triterpenic compounds that abound in industrial olive oil waste. These compounds have renowned antimicrobial properties and lack cytotoxicity in eukaryotic cells as well as resistance mechanisms in bacteria. Despite these advantages, their antimicrobial activity has only been tested in vitro, and derivatives improving this activity have not been reported. In this work, a set of 14 OA and MA C-28 amide derivatives have been synthesized. Two of these derivatives, MA-HDA and OA-HDA, increase the in vitro antimicrobial activity of the parent compounds while reducing their toxicity in most of the Gram-positive bacteria tested, including a methicillin-resistant Staphylococcus aureus-MRSA. MA-HDA also shows an enhanced in vivo efficacy in a Galleria mellonella invertebrate animal model of infection. A preliminary attempt to elucidate their mechanism of action revealed that these compounds are able to penetrate and damage the bacterial cell membrane. More significantly, their capacity to reduce antibiofilm formation in catheters has also been demonstrated in two sets of conditions: a static and a more challenged continuous-flow S. aureus biofilm.enantibiofilmin vitro and in vivo antimicrobialsmaslinic and oleanolic acidsnatural productsAnimalsBacterial Outer MembraneBiofilmsCross InfectionDisease Models, AnimalGram-Positive BacteriaGram-Positive Bacterial InfectionsLepidopteraMicrobial Sensitivity TestsMolecular StructureOleanolic AcidPentacyclic TriterpenesTriterpenesresearch article31268675Restricted AccessAnimalesBacterias grampositivasBiopelículasEstructura molecularInfecciones por bacteriasGrampositivasInfección hospitalariaLepidópterosMembrana externa bacterianaModelos animales de enfermedadPruebas de sensibilidadMicrobianaTriterpenosTriterpenos pentacíclicosÁcido oleanólico10.1021/acsinfecdis.9b001252373-8227https://pubs.acs.org/doi/pdf/10.1021/acsinfecdis.9b00125