Synthesis of pyrimidine-2,4,6-trione derivatives: Anti-oxidant, anti-cancer, α-glucosidase, β-glucuronidase inhibition and their molecular docking studies

Assem Barakat; Mohammad Shahidul Islam; Abdullah Mohammed Al-Majid; Hazem A Ghabbour; Sammer Yousuf; Mahwish Ashraf; Nimra Naveed Shaikh; M Iqbal Choudhary; Ruqaiya Khalil; Zaheer Ul-Haq

doi:10.1016/j.bioorg.2016.07.009

Synthesis of pyrimidine-2,4,6-trione derivatives: Anti-oxidant, anti-cancer, α-glucosidase, β-glucuronidase inhibition and their molecular docking studies

Bioorg Chem. 2016 Oct:68:72-9. doi: 10.1016/j.bioorg.2016.07.009. Epub 2016 Jul 19.

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, P. O. Box 426, Ibrahimia, 21321 Alexandria, Egypt. Electronic address: ambarakat@ksu.edu.sa.
² Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
⁴ H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
⁵ Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia; H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
⁶ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.

PMID: 27454620
DOI: 10.1016/j.bioorg.2016.07.009

Abstract

This paper describes a facile protocol, efficient, and environmentally benign for the synthesis a series of barbiturate acid substituted at C5 position 3a-o. The desired compounds subjected in vitro for different set of bioassays including against anti-oxidant (DPPH and super oxide scavenger assays), anti-cancer, α-glucosidase and β-glucuronidase inhibitions. Compound 3m (IC50=22.9±0.5μM) found to be potent α-glucosidase enzyme inhibitors and showed more activity than standard acarbose (IC50=841±1.73μM). Compound 3f (IC50=86.9±4.33μM) found to be moderate β-Glucuronidase enzyme inhibitors and showed activity comparatively less than the standard d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Furthermore, in sillico investigation was carried out to investigate bonding mode of barbiturate acid derivatives.

Keywords: Anti-cancer; Anti-oxidant; Pyrimidine-2,4,6-trione; α-Glucosidase inhibitor; β-Glucuronidase inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Antioxidants / chemical synthesis
Antioxidants / chemistry
Antioxidants / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Glucuronidase / antagonists & inhibitors*
Glucuronidase / metabolism
Glycoproteins / chemical synthesis
Glycoproteins / chemistry
Glycoproteins / pharmacology*
HeLa Cells
Humans
Mice
Molecular Docking Simulation*
Molecular Structure
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry
Pyrimidinones / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Antioxidants
Glycoproteins
Pyrimidinones
beta-glucuronidase inhibitor
pyrimidine-2,4,6-trione
Glucuronidase