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

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