title: Unusual biotransformation products of the sesquiterpene lactone budlein A by Aspergillus species.
abstract: Biotransformation of chemicals by microorganisms can be effective in increasing chemical diversity. Some fungi have been described to be useful for the biotransformation of sesquiterpene lactones. Nevertheless, in most cases, only minor or simple transformations of functional groups have been observed. Budlein A is a sesquiterpene lactone found in high amounts in American sunflower-like species of the genus Viguiera (Asteraceae). It shows important biological effects like in vitro and in vivo anti-inflammatory activity, as well as cytotoxicity against cancer cell lines. With the aim to obtain potentially bioactive derivatives of budlein A and taking into account that obtaining semi-synthetic analogues is a very complex task, the capability of soil fungi to promote biotransformation was investigated. In this work, the biotransformation of budlein A by the soil fungi Aspergillus terreus and A. niger affording three unusual sesquiterpenoid derivatives with carbon skeletons is reported. The chemical structures of the compounds were elucidated by 1D and 2D NMR spectrometry and HR-ESI-MS. The stereochemistry and molecular conformation of one derivative was assessed by molecular modeling techniques. The fungal metabolites displayed a reduced cytotoxicity against HL-60 cells when compared to the original natural product. The results show the versatility of microbial-catalyzed biotransformations leading to unusual derivatives.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil; Universidade Estadual de Londrina, Av. Robert Koch 60, 86039-440 Londrina, PR, Brazil.
authors.forename: Nilton Syogo
authors.initials: NS
authors.lastname: Arakawa
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gobbo-Neto
authors.forename: Sérgio Ricardo
authors.initials: SR
authors.lastname: Ambrosio
authors.forename: Gilmara Ausech
authors.initials: GA
authors.lastname: Antonucci
authors.forename: Suely Vilela
authors.initials: SV
authors.lastname: Sampaio
authors.forename: Mônica Tallarico
authors.initials: MT
authors.lastname: Pupo
authors.forename: Suraia
authors.initials: S
authors.lastname: Said
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Schmidt
authors.forename: Fernando Batista
authors.initials: FB
authors.lastname: Da Costa
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001230:Aspergillus / Q000254:growth & development / Q000378:metabolism*; D019659:Asteraceae / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology; D001711:Biotransformation; D055088:Early Detection of Cancer; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D012988:Soil Microbiology; D013237:Stereoisomerism
chemical_list: D000893:Anti-Inflammatory Agents; D007783:Lactones; D012717:Sesquiterpenes; C520233:budlein A
keywords: Aspergillus; Budlein A; Cytotoxic activity; Microbial transformation; Sesquiterpene lactones; Viguiera robusta