Synthesis and antihepatotoxic activity of dihydropyrimidinone derivatives linked with 1,4-benzodioxane

Abstract

Purpose:

To evaluate the antihepatotoxic activity of dihydropyrimidinone derivative linked with 1,4-benzodioxane.

Methods:

A series of novel dihydropyrimidinone derivatives linked with 1,4-benzodioxane moiety were synthesized in good yield. Modern spectroscopic techniques and elemental analysis were used for the identification of the synthesized compounds. The hepatoprotective properties of compound 2, 4-(4-nitrophenyl)-5-(2,3-dihydro-1,4-benzodioxin-6-ylcarbonyl)-3,4-dihydropyrimidin-2(1H)-one, was evaluated in a carbon tetrachloride (CCl₄)-induced hepatotoxicity rat model.

Results:

Administration of compound 2 prior to CCl₄ exposure produced a dose-dependent decrease in the levels of elevated biochemical parameters compared with the standard drug silymarin. CCl₄ induced oxidative stress, increased lipid profile, and decreased high-density lipoprotein (HDL) levels. Compound 2 (20 mg/kg) significantly reduced the lipid profile and significantly improved HDL levels in a dose-dependent manner. CCl₄ treatment increased malondialdehyde (MDA) level and decreased nonprotein thiol (NP-SH) and total protein (TP) in liver tissues. Pretreatment of rats with compound 2 (20 mg/kg) decreased MDA level and increased NP-SH and TP in liver tissues. Histopathological examination of liver tissues also confirmed the hepatoprotective activity of compound 2.

Conclusion:

These results demonstrate the antihepatotoxic activity of compound 2 in CCl₄-induced hepatotoxicity model.

Keywords:

• antihepatotoxic activity
• dihydropyrimidinone
• 14-benzodioxane
• carbon tetrachloride
• silymarin

Acknowledgments

The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding this research group no. (RG 1435-006).

Disclosure

The authors report no conflicts of interest in this work.