DESIGN, SYNTHESIS AND COX1/2 INHIBITORY ACTIVITY OF NEW QUINAZOLINE-5-ONE DERIVATIVES

Authors

  • Ahmed S. Aboraia epartment of Medicinal Chemistry, Faculty of Pharmacy, Assuit University, 71524, Assuit, Egypt.
  • Mohammed A. Hara Department of Organic Chemistry, Faculty of pharmacy, Al-azhar University, Assuit Branch, 71524, Assuit, Egypt.
  • Mostafa H. Abdelrahman Department of Organic Chemistry, Faculty of pharmacy, Al-azhar University, Assuit Branch, 71524, Assuit, Egypt.
  • Mohamed M. Amin Department of Organic Chemistry, Faculty of Pharmacy, Suez Canal University, 41522, Ismailia, Egypt.
  • Osama I. El-Sabbaghab Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.

DOI:

https://doi.org/10.24297/jac.v13i12.6019

Keywords:

COX-2 selective, Quinazolinone, COX-1/2 Inhibitory, Docking

Abstract

A new series of 1-(4-Acetylphenyl)-7,7-dimethyl-3-(substitutedphenyl)-1,2,3,4,7,8-octahydroquinazolin-5(6H)-ones (6-15) were synthesized and tested against COX-1 and COX-2 enzymes. Those compounds exhibited strong interaction at the COX-2 binding site and poor interaction at the COX-1 active site. Subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assay; most of the compounds especially compounds 6, 7, 12, 13, and 16 exhibited potent anti-inflammatory effects, selective COX-2 inhibition, with half-maximal inhibitor concentration (IC50) values of 0.22–1.42 μM and selectivity index (SI) values of 6.16–14.18 compared with celecoxib (IC50 = 0.05 μM and COX-2 SI: 296), diclofenac (IC50 = 0.8 μM and COX-2 SI: 4.87), and indomethacin (IC50 = 0.49 μM and COX-2 SI: 0.08) as reference drugs. Docking study has been carried out to confirm the binding affinity and selectivity of the most active compound (compound 6) to COX-2 enzyme.

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References

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Published

2017-04-12

How to Cite

Aboraia, A. S., Hara, M. A., Abdelrahman, M. H., M. Amin, M., & El-Sabbaghab, O. I. (2017). DESIGN, SYNTHESIS AND COX1/2 INHIBITORY ACTIVITY OF NEW QUINAZOLINE-5-ONE DERIVATIVES. JOURNAL OF ADVANCES IN CHEMISTRY, 13(1), 5923–5931. https://doi.org/10.24297/jac.v13i12.6019

Issue

Vol. 13 No. 1 (2017)

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Articles

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