Structure-Activity Relationship and Molecular Docking of Quinazolinones Inhibiting Expression of COX-2, IL-1β, iNOS, and TNF-α through NF-κB Pathways

Sutthichat Kerdphon; Nopawit Khamto; Kittisak Buddhachat; Jatuporn Ngoenkam; Pussadee Paensuwan; Sutatip Pongcharoen; Thishana Singh; Puttinan Meepowpan; Jira Jongcharoenkamol

doi:10.1021/acsmedchemlett.3c00098

Structure-Activity Relationship and Molecular Docking of Quinazolinones Inhibiting Expression of COX-2, IL-1β, iNOS, and TNF-α through NF-κB Pathways

ACS Med Chem Lett. 2023 Aug 15;14(9):1167-1173. doi: 10.1021/acsmedchemlett.3c00098. eCollection 2023 Sep 14.

Authors

Affiliations

¹ Department of Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand.
² Center of Excellence in Petroleum, Petrochemicals and Advanced Materials, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand.
³ Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai 50200, Thailand.
⁴ Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand.
⁵ Department of Biology, Faculty of Science, Naresuan University, Phitsanulok 65000, Thailand.
⁶ Department of Microbiology and Parasitology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
⁷ Department of Optometry, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand.
⁸ Department of Medicine, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand.
⁹ School of Chemistry and Physics, University of Kwazulu-Natal, Private Bag X54001, Durban 4000, South Africa.
¹⁰ Center of Excellence in Material Science and Technology, Chiang Mai University, Chiang Mai 50200, Thailand.
¹¹ Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Science, Naresuan University, Phitsanulok 65000, Thailand.

PMID: 37736179
PMCID: PMC10510524 (available on 2024-09-14)
DOI: 10.1021/acsmedchemlett.3c00098

Abstract

The quinazolinone scaffold is found in natural products and biologically active compounds, including inflammatory inhibitors. Major proteins or enzymes involved in the inflammation process are regulated by the amount of gene expression. Quinazolinone derivatives were investigated and developed against the inflammatory genes cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cell line. The mRNA expressions were measured using a real-time quantitative polymerase chain reaction (RT-qPCR). Quinazolinone compounds at 62.5 μM demonstrated anti-COX-2 and anti-IL-1β mRNA expressions down to 0.50% and 3.10% gene expression, respectively, via inhibition of nuclear factor κB (NF-κB). Molecular docking was performed to explain the interaction between the binding site and the developed compounds as well as the structure-activity relationship of the quinazolinone moiety.