Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones

Khalid Mohammed Khan; Syed Muhammad Saad; Nimra Naveed Shaikh; Shafqat Hussain; Muhammad Imran Fakhri; Shahnaz Perveen; Muhammad Taha; Muhammad Iqbal Choudhary

doi:10.1016/j.bmc.2014.04.039

Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones

Bioorg Med Chem. 2014 Jul 1;22(13):3449-54. doi: 10.1016/j.bmc.2014.04.039. Epub 2014 Apr 26.

Authors

Khalid Mohammed Khan¹, Syed Muhammad Saad², Nimra Naveed Shaikh², Shafqat Hussain², Muhammad Imran Fakhri², Shahnaz Perveen³, Muhammad Taha⁴, Muhammad Iqbal Choudhary⁵

Affiliations

¹ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: hassaan2@super.net.pk.
² H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
³ PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. Salimuzzaman Siddiqui, Karachi 75280, Pakistan.
⁴ Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam Campus, 42300, Malaysia.
⁵ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah 2254, Saudi Arabia.

PMID: 24844756
DOI: 10.1016/j.bmc.2014.04.039

Abstract

2-Arylquinazolin-4(3H)-ones 1-25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1-25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6-198.2μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6-44.0μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure-activity relationship is established.

Keywords: 2-Arylquinazolin-4(3H)-ones; Cytotoxicity; Structure–activity relationship; β-Glucuronidase inhibition.

Publication types

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

MeSH terms

Dose-Response Relationship, Drug
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Escherichia coli / enzymology
Glucuronidase / metabolism*
Molecular Structure
Structure-Activity Relationship

Substances

Enzyme Inhibitors
Glucuronidase