title: Quantitative structure-activity relationship of molecules constituent of different essential oils with antimycobacterial activity against Mycobacterium tuberculosis and Mycobacterium bovis.
abstract: BACKGROUND
  Essential oils and their constituents are commonly known for their antibacterial, antifungal and antiparasitic activity, and there are also reports on the antimycobacterial properties, but more experimental data are needed for the description of the mechanism of action or structural (and molecular) properties related to the antimicrobial activity.
  
  
  METHODS
  Twenty-five constituents of essential oils were evaluated against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis AN5 by the Alamar Blue technique. Twenty compounds were modeled using in silico techniques descriptor generation and subsequent QSAR model building using genetic algorithms. The p-cymene, menthol, carvacrol and thymol were studied at the quantum mechanical level through the mapping of HOMO and LUMO orbitals. The cytotoxic activity against macrophages (J774A) was also evaluated for these four compounds using the Alamar Blue technique.
  
  
  RESULTS
  All compounds tested showed to be active antimicrobials against M. tuberculosis. Carvacrol and thymol were the most active terpenes, with MIC values of 2.02 and 0.78 μg/mL respectively. Cinnamaldehyde and cinnamic acid were the most active phenylpropanes with MIC values of 3.12 and 8.16 μg/mL respectively. The QSAR models included the octanol-water partition (LogP) ratio as the molecular property that contributes the most to the antimycobacterial activity and the phenolic group (nArOH) as the major structural element.
  
  
  CONCLUSIONS
  The description of the molecular properties and the structural characteristics responsible for antimycobacterial activity of the compounds tested, were used for the development of mathematical models that describe structure-activity relationship. The identification of molecular and structural descriptors provide insight into the mechanisms of action of the active molecules, and all this information can be used for the design of new structures that could be synthetized as potential new antimycobacterial agents.
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario S/N. Campus Universitario II, Chihuahua, 31125, Chih., México.
authors.forename: Sergio
authors.initials: S
authors.lastname: Andrade-Ochoa
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario S/N. Campus Universitario II, Chihuahua, 31125, Chih., México.
authors.forename: Guadalupe Virginia
authors.initials: GV
authors.lastname: Nevárez-Moorillón
authors.affiliation: Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prolongación de Carpio y Plan de Ayala S/N, Col. Santo Tomas 11340, México, DF, México.
authors.forename: Luvia E
authors.initials: LE
authors.lastname: Sánchez-Torres
authors.affiliation: Asociación de Jubilados de la Universidad de Guanajuato, Guanajuato, Gto., México.
authors.forename: Manuel
authors.initials: M
authors.lastname: Villanueva-García
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario S/N. Campus Universitario II, Chihuahua, 31125, Chih., México.
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Sánchez-Ramírez
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario S/N. Campus Universitario II, Chihuahua, 31125, Chih., México.
authors.forename: Luz María
authors.initials: LM
authors.lastname: Rodríguez-Valdez
authors.affiliation: Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario S/N. Campus Universitario II, Chihuahua, 31125, Chih., México. bchavira@uach.mx.
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Rivera-Chavira
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000081007:Cymenes; D008826:Microbial Sensitivity Tests; D039821:Monoterpenes / Q000494:pharmacology; D009163:Mycobacterium bovis / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009822:Oils, Volatile / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013729:Terpenes / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000081007:Cymenes; D039821:Monoterpenes; D009822:Oils, Volatile; D013729:Terpenes; C007210:4-cymene; C073316:carvacrol