Phenylisoxazole-3/5-Carbaldehyde Isonicotinylhydrazone Derivatives: Synthesis, Characterization, and Antitubercular Activity: Synthesis, Characterization, and Antitubercular Activity

Eight new phenylisoxazole isoniazid derivatives, 3-(2′-fluorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (1), 3-
(2′-methoxyphenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (2), 3-(2′-chlorophenyl)isoxazole-5-carbaldehyde
isonicotinylhydrazone (3), 3-(3′-clorophenyl)isoxazole-5-carbaldehyde isonicotinylhydrazone (4), 3-(4′-bromophenyl)
isoxazole-5-carbaldehyde isonicotinylhydrazone (5), 5-(4′-methoxiphenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (6), 5-
(4′-methylphenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone (7), and 5-(4′-clorophenyl)isoxazole-3-carbaldehyde isonicotinylhydrazone
(8), have been synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR, and mass spectral data. The 2D
NMR (1H-1H NOESY) analysis of 1 and 2 confirmed that these compounds in acetone-d6 are in the trans(E) isomeric form. This
evidence is supported by computational calculations which were performed for compounds 1–8, using DFT/B3LYP level with the 6-
311++G(d,p) basis set. The in vitro antituberculous activity of all the synthesized compounds was determined against the Mycobacterium
tuberculosis standard strains: sensitive H37Rv (ATCC-27294) and resistant TB DM97. All the compounds exhibited
moderate bioactivity (MIC= 0.34–0.41 μM) with respect to the isoniazid drug (MIC =0.91 μM) against the H37Rv sensitive strain.
Compounds 6 (X= 4′-OCH3) and 7 (X= 4′-CH3) with MIC values of 12.41 and 13.06 μM, respectively, were about two times more
cytotoxic, compared with isoniazid, against the resistant strain TB DM97.