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

Authors Bhat MA, Al-Omar MA, Khan AA, Alanazi AM, Naglah AM

Received 23 December 2018

Accepted for publication 4 April 2019

Published 18 July 2019 Volume 2019:13 Pages 2393—2404


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Editor who approved publication: Dr Tuo Deng

Mashooq Ahmad Bhat,1 Mohamed A Al-Omar,1 Azmat Ali Khan,1 Amer M Alanazi,1 Ahmed M Naglah2,3

1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 2Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 3Peptide Chemistry Department, Chemical Industries Research Division, National Research, Centre, Cairo, Egypt

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

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