title: Detection of synergistic combinations of Baccharis extracts with terbinafine against Trichophyton rubrum with high throughput screening synergy assay (HTSS) followed by 3D graphs. Behavior of some of their components.
abstract: Forty four extracts from nine Baccharis spp. from the Caulopterae section were tested in combination with terbinafine against Trichophyton rubrum with the HTSS assay at six different ratios with the aim of detecting those mixtures that produced a ≥50% statistically significant enhancement of growth inhibition. Since an enhanced effect of a combination respective of its components, does not necessarily indicate synergism, three-dimensional (3D) dose-response surfaces were constructed for each selected pair of extract/antifungal drug with the aid of CombiTool software. Ten extracts showed synergistic or additive combinations which constitutes a 22% hit rate of the extracts submitted to evaluation. Four flavonoids and three ent-clerodanes were detected in the active Baccharis extracts with HPLC/UV/ESI-MS methodology, all of which were tested in combination with terbinafine. Results showed that ent-clerodanes but not flavonoids showed synergistic or additive effects. Among them, bacchotricuneatin A followed by bacrispine showed synergistic effects while hawtriwaic acid showed additive effects.
authors.affiliation: Pharmacognosy Area, School of Biochemical and Pharmaceutical Sciences, National University of Rosario, Suipacha 531, 2000 Rosario, Argentina; Vegetal Biology Area, School of Biochemical and Pharmaceutical Sciences, National University of Rosario, Suipacha 531, 2000 Rosario, Argentina.
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Rodriguez
authors.forename: Maximiliano A
authors.initials: MA
authors.lastname: Sortino
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Ivancovich
authors.forename: José M
authors.initials: JM
authors.lastname: Pellegrino
authors.forename: Laura S
authors.initials: LS
authors.lastname: Favier
authors.forename: Marcela P
authors.initials: MP
authors.lastname: Raimondi
authors.forename: Martha A
authors.initials: MA
authors.lastname: Gattuso
authors.forename: Susana A
authors.initials: SA
authors.lastname: Zacchino
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001118:Argentina; D031175:Baccharis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D057166:High-Throughput Screening Assays / Q000379:methods*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009281:Naphthalenes / Q000494:pharmacology*; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012984:Software; D021241:Spectrometry, Mass, Electrospray Ionization; D000077291:Terbinafine; D014249:Trichophyton / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000935:Antifungal Agents; D045785:Diterpenes, Clerodane; D005419:Flavonoids; D009281:Naphthalenes; D010936:Plant Extracts; D000077291:Terbinafine
keywords: 3D surface–response curves; Additivism; Antifungal; Baccharis species; CombiTool software; Ent-clerodanes; Flavonoids; High throughput screening synergy assay; Synergism; Terbinafine; Trichophyton rubrum