title: Flavonoids from Piper delineatum modulate quorum-sensing-regulated phenotypes in Vibrio harveyi.
abstract: Quorum sensing (QS), or bacterial cell-to-cell communication, is a key process for bacterial colonization of substrata through biofilm formation, infections, and production of virulence factors. In an ongoing investigation of bioactive secondary metabolites from Piper species, four new flavonoids (1-4), along with five known ones (5-9) were isolated from the leaves of Piper delineatum. Their stereostructures were established by spectroscopic and spectrometric methods, including 1D and 2D NMR experiments, and comparison with data reported in the literature. The compounds were screened for their ability to interfere with QS signaling in the bacterial model Vibrio harveyi. Four compounds from this series (2, 3, 6, and 7) exhibited remarkable activity in the micromolar range, being compounds 3 and 7 particularly attractive since they did not affect bacterial growth. The results suggest that these flavonoids disrupt QS-mediated bioluminescence by interaction with elements downstream LuxO in the QS circuit of V. harveyi, and also, they exhibited a strong dose-dependent inhibition of biofilm formation. The present findings shed light on the QS inhibition mechanisms of flavonoids, underlining their potential applications.
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain; Plataforma Oceánica de Canarias (PLOCAN), Carretera de Taliarte s/n, 35214 Telde, Gran Canaria, Spain.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Martín-Rodríguez
authors.affiliation: Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticas y Bioquímicas, Universidad Mayor de San Andrés, Avenida. Saavedra 2224, Miraflores, La Paz, Bolivia.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Ticona
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Jiménez
authors.affiliation: Instituto de Investigaciones Fármaco Bioquímicas, Facultad de Ciencias Farmacéuticas y Bioquímicas, Universidad Mayor de San Andrés, Avenida. Saavedra 2224, Miraflores, La Paz, Bolivia.
authors.forename: Ninoska
authors.initials: N
authors.lastname: Flores
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain. Electronic address: jjfercas@ull.es.
authors.forename: José J
authors.initials: JJ
authors.lastname: Fernández
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain. Electronic address: ilopez@ull.es.
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Bazzocchi
mesh_terms: D018441:Biofilms / Q000187:drug effects; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010568:Peru; D010641:Phenotype; D031701:Piper / Q000737:chemistry* / Q000382:microbiology; D018515:Plant Leaves / Q000737:chemistry; D053038:Quorum Sensing; D014733:Vibrio / Q000378:metabolism / Q000502:physiology*
chemical_list: D005419:Flavonoids
keywords: Biofilm; Flavonoids; Piper delineatum; Quorum sensing; Vibrio harveyi