EFFICACIOUS SYNTHESIS, IN VIVO ANTI-INFLAMMATORY AND IN VITRO ANTITUBERCULAR ACTIVITY OF NOVEL PYRIDAZINONES AND THEIR EXPECTED ANTI-INFLAMMATORY MECHANISM

Bhawna Sharma,* and Upendra K. Sharma

ABSTRACT

A new series of 2-(5-amino-1,3,4 thiadiazol-2-yl)methyl)-6-phenyl-4,5-dihydropyridazin-3(2H)-one derivatives has been synthesized and evaluated for their In-vitro antitubercular and In-vivo anti-inflammatory activity. Antitubercular activity of synthesized compounds were screened by serial dilution method and disc diffusion method using middlebrook 7H9 medium (broth and agar based) and ATCC 25175 strain of M.Tuberculosis. The anti-inflammatory activity of the synthesized compounds was studied using a carageenan-induced hind paw edema model in rat. Test compounds (100 mg/Kg) and indomethacine (10 mg/Kg) dose level were administered orally to the experimental animals. All pyridazinone derivatives bearing acetic acid hydrazide moieties (1c, 1e, 3c) showed remarkably potent anti-inflammatory activity, especially after 3 and 4hr the drug was administered, but compounds containing P-chlorophenyl group substitution in aromatic ring in the structure (5c, 5d & 5e ) had the most potent anti-inflammatory agents. Derivatives with 4-ethyl phenyl substitution (2e) and chloro phenyl substitution (5d, 5e) at p-position of pyridazinone nuclei showed good antitubercular activity with MIC value of 1.25 μg/ml then other aryl substitution like 4-methoxy phenyl 1d &1e, 4-methyl phenyl 3d & 3e with MIC value of 3.125 & 2.5 μg/ml.

Keywords: Pyridazinone, anti-inflammatory agents, Antitubercular agents, Paw edema model, Aryl-substituted pyridazinones.