Synthetic Novel 1, 4- Dihydropyridine Derivatives Act as Potential Hepatoprotective Agent against CCl4 Induced Rat Hepatocytes

Abstract

The objective of the present work was the synthesis of 1-(5-acetyl-4 (4-substituted phenyl)-2, 6-dimethyl-1,4-dihydroxypyridine-3-yl)-ethan-1-one and evaluation of in vivo hepatoprotective activity. Based on this a new series of compound had been planned to synthesize by reacting acetyl acetone with various aromatic aldehydes in the presence of ammonium acetate. The synthesized compounds were characterized by IR, NMR, and Mass spectroscopy. The in-vivo Hepatoprotective activity was carried out by using albino rats. The results displayed that the elevated levels of SGOT, SGPT, ALP and Serum bilirubin were mainly due to CCl4 intoxication, reduced significantly (*P < 0.05) in rats, after treatment with synthesized compounds. Treatment with a synthesized compound at a dose of 250 mg/kg b.w. decreased the SGOT, SGPT, ALP, Serum bilirubin levels by 6.23% ns (non significantly), 28.96%, 8.81%, and 11.11% ns (non significantly) respectively, while a higher dose of 500 mg/kg b. wt. was more effective, causing a reduction of 25.02%, 47.65%, 24.09% and 27.35%. Silymarin was used as standard drug showed a reduction of 55.09%, 68.98%, 57.46% and 35.04% receiving CCl4 alone. So depending upon the experimental data it was confirmed that the biochemical parameters of the group treated with compounds were significantly lower than the CCl4 treated group. Moreover the treatment with the synthesized compounds significantly reduced the previously raised levels of AST, ALT, ALP and bilirubin in hepatotoxic rats. Histopathological investigation displayed that at both doses (250 mg/kg b.w. and 500 mg/kg b.w.) the synthesized compounds were possessed moderate to good hepatoprotective activity, but at 500 mg/kg b.w. executed excellent hepatoprotective activity against CCl4 induced damaged hepatocytes.