title: Synthesis of pyrimidine-2,4,6-trione derivatives: Anti-oxidant, anti-cancer, α-glucosidase, β-glucuronidase inhibition and their molecular docking studies.
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.
authors.affiliation: 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.
authors.forename: Assem
authors.initials: A
authors.lastname: Barakat
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammad Shahidul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdullah Mohammed
authors.initials: AM
authors.lastname: Al-Majid
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Ghabbour
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Sammer
authors.initials: S
authors.lastname: Yousuf
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Mahwish
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Nimra Naveed
authors.initials: NN
authors.lastname: Shaikh
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Iqbal Choudhary
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Ruqaiya
authors.initials: R
authors.lastname: Khalil
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Zaheer
authors.initials: Z
authors.lastname: Ul-Haq
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005966:Glucuronidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006023:Glycoproteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D006023:Glycoproteins; D011744:Pyrimidinones; C011473:beta-glucuronidase inhibitor; C000620878:pyrimidine-2,4,6-trione; D005966:Glucuronidase
keywords: Anti-cancer; Anti-oxidant; Pyrimidine-2,4,6-trione; α-Glucosidase inhibitor; β-Glucuronidase inhibitor