Evaluation of Dual 5-Lipoxygenase/Microsomal Prostaglandin E2 Synthase-1 Inhibitory Effect of Natural and Synthetic Acronychia-Type Isoprenylated Acetophenones


Among the pathways responsible for the development of inflammatory responses, the cyclooxygenase and lipoxygenase pathways are among the most important ones. Two key enzymes, namely, 5-LO and mPGES-1, are involved in the biosynthesis of leukotrienes and prostaglandins, respectively, which are considered attractive therapeutic targets, so their dual inhibition might be an effective strategy to control inflammatory deregulation. Several natural products have been identified as 5-LO inhibitors, with some also being dual 5-LO/mPGES-1 inhibitors. Here, some prenylated acetophenone dimers from Acronychia pedunculata have been identified for their dual inhibitory potency toward 5-LO and mPGES-1. To gain insight into the SAR of this family of natural products, the synthesis and biological evaluation of analogues are presented. The results show the ability of the natural and synthetic molecules to potently inhibit 5-LO and mPEGS-1 in vitro. The potency of the most active compound (10) has been evaluated in vivo in an acute inflammatory mouse model and displayed potent anti-inflammatory activity comparable in potency to the drug zileuton used as a positive control.

SEEK ID: https://data.chembiosys.de/publications/42

PubMed ID: 28240894

Projects: A4, Total ChemBioSys

Publication type: Not specified

Journal: J Nat Prod

Citation: J Nat Prod. 2017 Mar 24;80(3):699-706. doi: 10.1021/acs.jnatprod.6b01008. Epub 2017 Feb 27.

Date Published: 28th Feb 2017

Registered Mode: Not specified

Authors: A. Svouraki, U. Garscha, E. Kouloura, S. Pace, C. Pergola, V. Krauth, A. Rossi, L. Sautebin, M. Halabalaki, O. Werz, N. Gaboriaud-Kolar, A. L. Skaltsounis

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Created: 8th May 2017 at 10:13

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