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

Abstract

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 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.

Keywords

• Anti-inflammatory activity
• Analgesic activity
• Antipyretic activity
• Hypotonicity-induced haemolysis
• Albumin denaturation