Identification of (4-chlorophenyl)(5-hydroxynaphtho[1,2-b]furan-3-yl)methanone as novel COX-2 inhibitor with analgesic profile

Shilong Hu; Wencheng Liu; Yu Gan; Xi Yang; Yanfang Wang; Xing Wei; Meiyuan Chen; Di Zhang; Bowen Ke

doi:10.1016/j.bmcl.2024.129631

Identification of (4-chlorophenyl)(5-hydroxynaphtho[1,2-b]furan-3-yl)methanone as novel COX-2 inhibitor with analgesic profile

Bioorg Med Chem Lett. 2024 Mar 1:100:129631. doi: 10.1016/j.bmcl.2024.129631. Epub 2024 Feb 1.

Authors

Shilong Hu¹, Wencheng Liu¹, Yu Gan¹, Xi Yang², Yanfang Wang¹, Xing Wei³, Meiyuan Chen¹, Di Zhang¹, Bowen Ke⁴

Affiliations

¹ Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
² Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
³ Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
⁴ Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. Electronic address: bowenke@scu.edu.cn.

PMID: 38307442
DOI: 10.1016/j.bmcl.2024.129631

Abstract

Chronic pain is a serious problem that affects billions of people worldwide, but current analgesic drugs limit their use in chronic pain management due to their respective side effects. As a first-line clinical drug for chronic pain, COX-2 selective inhibitors can relieve mild to moderate pain, but they also have some problems. The most prominent one is that their analgesic intensity is not enough, and they cannot well meet the treatment needs of chronic pain. Therefore, there is an urgent need to develop COX-2 inhibitors with stronger analgesic intensity. In this article, we used virtual screening method to screen out the structurally novel COX-2 inhibitor for chronic pain management, and conducted a preliminary study on its mechanism of action using molecular dynamics simulation.

Keywords: COX-2; Chronic pain; Inflammatory pain; Virtual screening.

MeSH terms

Analgesics / pharmacology
Analgesics / therapeutic use
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Chronic Pain* / drug therapy
Cyclooxygenase 2 Inhibitors* / pharmacology
Cyclooxygenase 2 Inhibitors* / therapeutic use
Furans
Humans

Substances

Cyclooxygenase 2 Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Furans