Citation: Fuyun Chi, Man Zhang, Yiman Han, Fukui Shen, Shijie Peng, Bo Su, Yuanyuan Hou, Gang Bai. Covalent modulation of mPGES1 activity via α,β-unsaturated aldehyde group: Implications for downregulating PGE2 expression and antipyretic response[J]. Chinese Chemical Letters, ;2025, 36(4): 109913. doi: 10.1016/j.cclet.2024.109913 shu

Covalent modulation of mPGES1 activity via α,β-unsaturated aldehyde group: Implications for downregulating PGE2 expression and antipyretic response

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China

houyy@nankai.edu.cn

gangbai@nankai.edu.cn

Received Date: 24 February 2024
Revised Date: 17 April 2024
Accepted Date: 19 April 2024
Available Online: 20 April 2024

Figures(7)

Prostaglandin E2 (PGE2) serves as the ultimate mediator of fever induced by inflammatory factors. In contrast to cyclooxygenase inhibitors that suppress arachidonic acid metabolism, antipyretic herbs possess a well-established clinical history in effectively managing fever. However, the specific mechanisms underlying their efficacy remain unclear. Following the screening for lead compounds that inhibit PGE2 from antipyretic herbs, alkynylated active molecule probes were designed and synthesized to track and identify potential targets. The target investigation revealed that three antipyretic compounds, namely cinnamaldehyde, 2,4-decadienal, and perillaldehyde, containing α,β-unsaturated aldehyde groups irreversibly targeted the microsomal PGES1-TM4 helix (mPGES1-TM4) at Ser139. This specific interaction effectually inhibited PGE2 production in the cerebral vasculature, leading to exert potent antipyretic effects. α,β-Unsaturated aldehydes targeting mPGES1-TM4 offer a new approach for antipyretic effects with significant potential for various applications.
- α,β-Unsaturated aldehyde,
- Covalent binding,
- mPGES1,
- PGE2,
- Antipyretic
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