Synthesis, characterization, and in vitro anti-Mycobacterium tuberculosis activity of terpene Schiff bases

A novel series of Schiff bases (3-13) were synthesized by the reaction of isoniazid (INH), nalidixic acid hydrazide, and fenamic acid hydrazides with monoterpenes (citral, camphor, and carvone) to obtain anti-mycobacterial agents in good yield and purity. The structures of the compounds were confirmed on the basis of their elemental analysis and spectral data. The structural modification of INH, nalidixic acid hydrazide, and fenamic acid hydrazides provided lipophilic adaptation of the respective hydrazides. The anti-mycobacterial activity of the synthesized compounds was investigated against four Mycobacterium strains: M. intercellulari (ATCC 35743), M. xenopi (ATCC 14470), M. cheleneo (ATCC 35751), and M. smegmatis (ATCC 35797). Compound 5, N'-[(1E)-2-methyl-5-(prop-1-en-2-yl) cyclohex-2-en-1-ylidene] pyridine-4-carbohydrazide with minimum inhibitory concentration (MIC 12 +/- A 0.03 mu g/mL) was found to be more potent than INH under the in vitro investigation conditions. It was found that there is no evident relation between the anti-tubercular activity of the tested compounds and their lipophilicity. However, lipophilicity has an influence on the activity, but it does not solely determine the anti-tubercular activity of these compounds. All compounds presented lipophilicity higher than that of respective parent hydrazide.