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

Abstract

BackgroundEssential 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.MethodsTwenty-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.ResultsAll 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.ConclusionsThe 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.

Natural Terpenes Influence the Activity of Antibiotics against Isolated Mycobacterium tuberculosis

“…The natural terpenes are known for their antimicrobial properties, and their detrimental effects on the structure and function of the microbial membranes and cell walls are thought to be evidence of antimicrobial action [4] . Combinations of essential oils and their constituents have been reported to have synergistic, additive, or inhibiting activity with antimicrobial interactions against several microorganisms [5] .…”

“…Combinations of essential oils and their constituents have been reported to have synergistic, additive, or inhibiting activity with antimicrobial interactions against several microorganisms [5] . A high antimycobacterial activity of thymol and carvacrol has been described against Mtb and Mycobacterium bovis [4] . Synergistic in vitro interactions between oleanolic acid and isoniazid, rifampicin, or ethambutol against Mtb have also been described [6] .…”

Pharmacological activities and medicinal properties of endemic Moroccan medicinal plant Origanum compactum (Benth) and their main compounds

“…Thymol possesses several biological effects such as antibacterial, antioxidant, antitumor, anti-inflammatory and antifungal activities [93,94]. The antibacterial effects of thymol have been evaluated by several studies [95][96][97][98][99][100] against E. coli and S. typhimurium and the MIC values against these two strains was respectively MIC = 1 and MIC = 1.2 mM [95]. The antibacterial activity of thymol against S. typhimurium has been also studied by Palaniappan and Holley [97] and Chauhan and Kang [98], and the MIC values were respectively MIC = 2.5 mM and MIC = 750 mM.…”

Essential oils and their components as an alternative in the control of mosquito vectors of disease

“…De hecho, el número de dobles enlaces conjugados contribuye a aumentar la actividad. Se ha reportado que el p-cimeno, el timol, el carvacrol y el eugenol exhiben mayor actividad que la carvona, los pinenos y los terpinenos (99), lo cual evidencia que la influencia de la densidad electrónica y el carácter plano de estas estructuras tienen un papel importante en su actividad biológica (125).…”

“…De hecho, en muchos casos estos orbitales determinan la reacción química de un compuesto y el posible mecanismo de ella (125). El orbital HOMO se emplea como un indicador de las zonas de alta densidad electrónica, pues estas exhiben una región propicia para el ataque de compuestos electrófilos, mientras que un reactivo o compuesto nucleófilo es atraído hacia las zonas de más baja densidad electrónica indicadas por el orbital LUMO (125).…”