Synthesis and biological evaluation of schiff bases of 4-aminophenazone as an anti-inflammatory, analgesic and antipyretic agent

A series of schiff base derivatives of 4-aminophenazone (4APZ-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one) with different aldehydes were synthesized. The synthetic compounds were screened for their anti-inflammatory, analgesic and antipyretic activities. The characterization of synthesized compounds was carried out by 1H NMR, 13C NMR and MS. Carrageenan-induced paw oedema (CIPO) and histamine induced paw oedema (HIPO) methods were used to determine the anti-inflammatory activity of commercial sample of 4APZ and its synthesized schiff bases in mice. The anti-inflammatory activity was in the order of 4APZAB > 4APZBB > 4APZCB > 4APZVn and all the test compounds exhibited considerable dose dependent inhibition of the paw oedema. The effect of the compounds on membrane stabilization was also determined which showed that compounds 4APZ (120 and 240 mg/kg doses), 4APZAB (160 mg/kg) and 4APZVn (600 mg/kg) produced highly significant inhibition (P < 0.001) of hypotonicity-induced haemolysis. Further, it was also observed that 4APZ (120 and 240 mg/kg doses), 4APZBB (500 mg/kg) and APZCB (150, 300 and 600 mg/kg dose) produced highly significant inhibition (P < 0.001) of albumin denaturation; a consistent dose dependent anti-inflammatory effect of test compounds as compared to the standard drug. Analgesic activity of the compounds was investigated by formalin-induced paw licking (FIPL) and acetic acid-induced writhing (AIW) methods in mice. It was observed that 4APZ (240 mg/kg), 4APZAB (160 mg/kg), 4APZBB (500 mg/kg), 4APZCB (600 mg/kg) and 4APZVn (600 mg/kg) showed analgesic effect with highly significant (P < 0.001) reduction of paw licking and writhing activity in the treated mice. The order of analgesic effect of the compounds was 4APZAB > 4APZBB > 4APZVn > 4APZCB. Moreover, phenobarbitone-induced sleeping time (PIST) in mice was also studied but only 600 mg/kg of 4APZVn significantly increased the duration of induced sleep which also suggested its sedative property. Brewer's yeast was used to induce fever in rabbits and analysed the compounds for their antipyretic activity. Different doses of 4APZ for different time durations (240 mg/kg-after 1 h, 120 and 240 mg/kg doses-after 2 h) produced highly significant (P < 0.001) inhibition of hyperpyrexia. Other compounds showed good antipyretic activity after 2, 3 and 4 h.