SYNTHESIS, CHARACTERIZATION AND IN VITRO ANTI-INFLAMMATORY ACTIVITY OF NOVEL PYRAZOLINE DERIVATIVES

Abstract

The objective of the present investigation to synthesize novel pyrazoline derivatives and assess the anti-inflammatory activity of the compounds. The pyrazoline derivatives (XI-XV) were synthesized in four sequential steps involving synthesis of dihyropyrimidine nucleus, followed by hydrazination of the carboethoxy group. The various chalcone molecules were prepared in the third step via claisen Schmidt condensation and finally the chalcone were cyclo-condensed to yield the pyrimidine-pyrazolinex compounds (XI-XV). The anti-inflammatory action of the synthesized compounds was determined using inhibition of albumin denaturation and inhibition of protease activity models. The products were soluble in chloroform and were obtained in 61-67% yield. In the IR spectrum, stretching bands of C-H (300-2840 cm-1), C=S (1818-1705 cm-1), C-C (1300-800 cm-1), C=N (1612-1602 cm-1) and C-S (950-850 cm-1) were observed in each compound. Bending vibration of N-H (1650-1580 cm-1) and C-N (1250-1020 cm-1) were also visible. The 1H-NMR spectra revealed protons of amine, methyl, acetyl and aromatic protons along with methylene of pyrazoline. All the compounds exhibited dose dependent inhibition of albumin denaturation with 6d having the highest capacity to cause the inhibition (67.2 %) at the concentration of 500μg/mL. The antiprotease action was also dose dependent and 6d at 500μg/mL was able to inhibit (48.3 %) of protease activity. The type of substitution on the terminal ring was found to affect the anti-inflammatory action in both the models.