title: Mutagenicity and antimutagenicity of (-)-hinokinin a trypanosomicidal compound measured by Salmonella microsome and comet assays.
abstract: BACKGROUND
  The dibenzylbutyrolactone lignan (-)-hinokinin (HK) was derived by partial synthesis from (-)-cubebin, isolated from the dry seeds of the pepper, Piper cubeba. Considering the good trypanosomicidal activity of HK and recalling that natural products are promising starting points for the discovery of novel potentially therapeutic agents, the aim of the present study was to investigate the (anti) mutagenic∕ genotoxic activities of HK.
  
  
  METHODS
  The mutagenic∕ genotoxic activities were evaluated by the Ames test on Salmonella typhimurium strains TA98, TA97a, TA100 and TA102, and the comet assay, so as to assess the safe use of HK in the treatment of Chagas' disease. The antimutagenic ∕antigenotoxic potential of HK were also tested against the mutagenicity of a variety of direct and indirect acting mutagens, such as 4- nitro-o-phenylenediamine (NOPD), sodium azide (SA), mitomycin C (MMC), benzo[a]pyrene (B[a]P), aflatoxin B1 (AFB1), 2-aminoanthracene (2-AA) and 2-aminofluorene (2-AF), by the Ames test, and doxorubicin (DXR) by the comet assay.
  
  
  RESULTS
  The mutagenicity∕genotoxicity tests showed that HK did not induce any increase in the number of revertants or extent of DNA damage, demonstrating the absence of mutagenic and genotoxic activities. On the other hand, the results on the antimutagenic potential of HK showed a strong inhibitory effect against some direct and indirect-acting mutagens.
  
  
  CONCLUSIONS
  Regarding the use of HK as an antichagasic drug, the absence of mutagenic effects in animal cell and bacterial systems is encouraging. In addition, HK may be a new potential antigenotoxic ∕ antimutagenic agent from natural sources. However, the protective activity of HK is not general and varies with the type of DNA damage-inducing agent used.
authors.affiliation: Departamento de Ciências Biológicas, UNESP-Universidade Estadual Paulista Julio de Mesquita Filho- Faculdade de Ciências Farmacêuticas de Araraquara, Araraquara, São Paulo, 14801-902, Brazil. flaviabiomed@yahoo.com.br
authors.forename: Flávia Aparecida
authors.initials: FA
authors.lastname: Resende
authors.forename: Lilian Cristina
authors.initials: LC
authors.lastname: Barbosa
authors.forename: Denise Crispim
authors.initials: DC
authors.lastname: Tavares
authors.forename: Mariana Santoro
authors.initials: MS
authors.lastname: de Camargo
authors.forename: Karen Cristina
authors.initials: KC
authors.lastname: de Souza Rezende
authors.forename: Márcio Luis de Andrade
authors.initials: ML
authors.lastname: E Silva
authors.forename: Eliana Aparecida
authors.initials: EA
authors.lastname: Varanda
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D052117:Benzodioxoles; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy; D020552:Comet Assay; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D009153:Mutagens / Q000494:pharmacology*; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D012475:Salmonella / Q000187:drug effects; D012639:Seeds / Q000737:chemistry; D014344:Trypanocidal Agents / Q000494:pharmacology*
chemical_list: D016587:Antimutagenic Agents; D052117:Benzodioxoles; D004149:Dioxoles; D017705:Lignans; D009153:Mutagens; D010936:Plant Extracts; D014344:Trypanocidal Agents; C475934:hinokinin; D015107:4-Butyrolactone