Quantitative structure-activity relationship of molecules constituent of different essential oils with antimycobacterial activity against Mycobacterium tuberculosis and Mycobacterium bovis

BMC Complementary and Alternative Medicine

Blanca E. Rivera-Chavira³  Luz María Rodríguez-Valdez³  Blanca E. Sánchez-Ramírez³  Manuel Villanueva-García²  Luvia E. Sánchez-Torres¹  Guadalupe Virginia Nevárez-Moorillón³  Sergio Andrade-Ochoa³ 

[1] Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Prolongación de Carpio y Plan de Ayala S/N, Col. Santo Tomas 11340, México, DF, México;Asociación de Jubilados de la Universidad de Guanajuato, Guanajuato, Gto., México;Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Circuito Universitario S/N. Campus Universitario II, Chihuahua 31125, Chih., México

关键词: Antimycobacterial activity;    QSAR;    Phenylpropanoids;    Terpenes;    Essential oils;   

Others  :  1233550
DOI  :  10.1186/s12906-015-0858-2

 received in 2015-04-15, accepted in 2015-09-11,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Andrade-Ochoa et al.

【 图 表 】

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