title: Reynosin and santamarine: two sesquiterpene lactones from Ambrosia confertiflora with bactericidal activity against clinical strains of Mycobacterium tuberculosis.
abstract: BACKGROUND
  Tuberculosis is primarily caused by Mycobacterium tuberculosis (Mtb). Previous studies have shown that the dichloromethanic extract of Ambrosia confertiflora DC (Asteraceae) inhibited Mtb.
  
  
  OBJECTIVE
  To isolate the compounds responsible for the mycobactericidal activity against clinical Mtb strains.
  
  
  METHODS
  The dichloromethanic extract of aerial parts of A. confertiflora was separated using chromatography columns. Mycobactericidal activity of the isolated compounds was evaluated using the Alamar Blue bioassay (128-16 μg/mL, 7 days). Cytotoxicity was tested against normal cell line L929 using the MTT ([3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium]) assay (100-3.125 μg/mL, 48 h). Compound structures were elucidated by1H and13C uni- and bidimensional NMR.
  
  
  RESULTS
  Two sesquiterpene lactones (SQLs) with mycobactericidal activity were identified: santamarine and reynosin. Reynosin was the most active compound, with a minimal bactericidal concentration (MBC) of 128 μg/mL against the H37Rv, 366-2009 and 104-2010 Mtb strains and a minimal inhibitory concentration (MIC) of 64, 64, 128, 128 and 128 μg/mL against the H37Rv, 104-2010, 63-2009, 366-2009 and 430-2010 Mtb strains, respectively. Santamarine had MBCs of 128 μg/mL against the H3Rv and 104-2010 Mtb strains and MICs of 128 μg/mL against the H37Rv, 366-2009 and 104-2010 Mtb strains. We also isolated 1,10-epoxyparthenolide but only showed mycobacteriostatic activity (MIC 128 μg/mL) against the Mtb strain. Compounds were tested against the L929 cell line and the calculated selectivity index was <1.
  
  
  CONCLUSIONS
  This is the first report of the mycobactericidal activity of these compounds against clinical Mtb strains. It is also the first report of the isolation of 1,10-epoxyparthenolide from A. confertiflora. The anti-mycobacterial activity of A. confertiflora was attributed to the SQLs identified.
authors.affiliation: a Departamento de Ciencias Químico Biológicas , Universidad de Sonora , Hermosillo , Sonora , México.
authors.forename: Enrique Wenceslao
authors.initials: EW
authors.lastname: Coronado-Aceves
authors.affiliation: a Departamento de Ciencias Químico Biológicas , Universidad de Sonora , Hermosillo , Sonora , México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Velázquez
authors.affiliation: a Departamento de Ciencias Químico Biológicas , Universidad de Sonora , Hermosillo , Sonora , México.
authors.forename: Ramón Enrique
authors.initials: RE
authors.lastname: Robles-Zepeda
authors.affiliation: b Instituto de Química, Universidad Nacional Autónoma de México , Distrito Federal , México.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jiménez-Estrada
authors.affiliation: c Unidad de Servicios de Apoyo en Resolución Analítica (SARA), Universidad Veracruzana , Xico, Veracruz , México.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernández-Martínez
authors.affiliation: a Departamento de Ciencias Químico Biológicas , Universidad de Sonora , Hermosillo , Sonora , México.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gálvez-Ruiz
authors.affiliation: a Departamento de Ciencias Químico Biológicas , Universidad de Sonora , Hermosillo , Sonora , México.
authors.forename: Adriana
authors.initials: A
authors.lastname: Garibay-Escobar
mesh_terms: D031164:Ambrosia / Q000737:chemistry*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D012717:Sesquiterpenes; C016722:santamarine; C016715:reynosin
keywords: 1,10-Epoxyparthenolide; mycobactericidal; sesquiterpenlactones