SCIENCE@home

1,4-Naphthoquinone Is a Potent Inhibitor of IRAK1 Kinases and the Production of Inflammatory Cytokines in THP-1 Differentiated Macrophages

I. Mahmoud,Ma’mon M. Hatmal,Duaa A. Abuarqoub,Ezaldeen Esawi,Hiba M. Zalloum,Suha Wehaibi,Hamdi Nsairat,W. Alshaer

Published 2021 in ACS Omega

ABSTRACT

Quinones are a class of cyclic organic compounds that are widely distributed in nature and have been shown to exhibit anti-inflammatory, antioxidant, and anticancerous activities. However, the molecular mechanisms/signaling by which these molecules exert their effect are still not fully understood. In this study, a group of quinone-derived compounds were examined for their potential inhibitory effect against human IRAK1 and IRAK4 kinases in vitro. We have identified five compounds: 1,4-naphthoquinone, emodin, shikonin, plumbagin, and menadione (vitamin K3) as active and selective inhibitors of human IRAK1 enzyme in vitro. The biochemical binding and molecular interactions between the active compounds and IRAK1’s catalytic site were demonstrated in silico using structural-based docking and dynamic simulation analysis. Also, 1,4-naphthoquinone was found to effectively inhibit the growth of cancer cell lines overexpressing IRAK1. Furthermore, 1,4-naphthoquinone potently suppressed the production and secretion of key proinflammatory cytokine proteins IL-8, IL-1β, IL-10, TNF-α, and IL-6 in LPS-stimulated PMA-induced human THP-1 macrophages. In conclusion, 1,4-naphthoquinone is an effective inhibitor of IRAK1 kinases and their mediated inflammatory cytokines production in LPS-stimulated PMA-induced human THP-1 macrophages.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-54 of 54 references · Page 1 of 1

CITED BY

Showing 1-26 of 26 citing papers · Page 1 of 1