1,4-Naphthoquinone: Biological Activity and Biomedical Applications

General Description

1,4-Naphthoquinone and its derivatives exhibit significant biological activities, including antimicrobial, cardioprotective, hepatoprotective, and anti-amyloid properties. Notable compounds like echinochrome enhance mitochondrial function, aid in liver health, and show promise in treating heart diseases and metabolic issues. Additionally, derivatives such as juglone have been utilized in innovative imaging techniques for cardiac necrosis, enabling rapid visualization of necrotic tissues. In neurology, novel derivatives have emerged as anti-amyloidogenic agents, capable of penetrating the blood-brain barrier, making them potential candidates for Alzheimer's disease imaging. Overall, 1,4-naphthoquinone demonstrates versatile therapeutic applications in medicine.

Figure 1. 1,4-Naphthoquinone

Biological Activity

Historical Overview

1,4-Naphthoquinone is a compound found naturally in several species across plants, animals, fungi, and bacteria. It is known for its significant biological activities, which include antimicrobial, antifungal, antiviral, and antitumor effects. One of the early naphthoquinones studied, lawsone, is derived from the henna shrub and is recognized primarily for its dyeing capabilities. Another naphthoquinone, juglone, originates from the Juglandaceae family and is notable for its antibacterial and fungicidal properties. Enhanced antimicrobial activities have been observed in synthetic derivatives of juglone, particularly those with hydrophobic substituents. Additionally, lapachol, a compound used in traditional Brazilian medicine, demonstrates anti-parasitic and anticancer properties due to its association with naphthoquinone. The diverse functionality of these compounds underlines the broad spectrum of biological activities associated with 1,4-naphthoquinones. ¹

Cardioprotective and Anti-ischemic Effects

The cardioprotective properties of 1,4-naphthoquinone derivatives such as polyhydroxynaphthoquinones are significant. Echinochrome, a derivative isolated from sea urchins, exemplifies this with its application in drugs like Histochrome, used in various medical fields including cardiology, ophthalmology, and pulmonary treatment. Echinochrome has been shown to enhance mitochondrial functions and assist in the regulation of calcium uptake in cardiac cells, which contributes to its effectiveness in treating heart-related ailments. Other related compounds, such as spinochrome D and U-441, have demonstrated protective effects against cytotoxicity and damage induced by ischemia in cell lines and animal models. These findings suggest that 1,4-naphthoquinone and its derivatives could offer new therapeutic strategies for managing heart disease. ¹

Hepatoprotective Properties

Echinochrome, a 1,4-naphthoquinone derivative, also displays hepatoprotective properties which are crucial in the management of liver diseases. Its administration has been linked to improved liver function through the reduction of liver enzyme activities and markers of oxidative stress. Echinochrome effectively combats hepatic oxidative stress, helps in repairing abnormal liver architecture, and acts as an alternative antiseptic remedy. In models of intrahepatic cholestasis, echinochrome demonstrates hepatoprotective and anticholestatic effects, characterized by decreased enzyme activities and enhanced liver function. Furthermore, this compound has shown potential in improving muscular functions and metabolic processes in diabetic patients, which reinforces the versatility and therapeutic potential of 1,4-naphthoquinone in medical applications. ¹

Biomedical Applications

Visualization of Cardiac Necrosis

1,4-Naphthoquinone and its derivatives, such as juglone, naphthazarin, plumbagin, and menadione, have been explored for their capability to rapidly visualize necrotic myocardium using iodine-131 radiolabeling. This innovative application has proven particularly effective in rat models with re-perfused myocardial infarction, where necrotic tissues could be distinctly visualized through SPECT/CT tomography as early as three hours post-injection. Among these, [131I]-naphthazarin displayed the highest necrotic-to-viable ratio, attributing its success to the direct binding with exposed DNA within necrotic tissues. This distinctive characteristic of 1,4-naphthoquinone derivatives highlights their potential as significant tools in the biomedical field, particularly in the diagnostic imaging of heart diseases where rapid and accurate detection of tissue viability is crucial. ^1,2

Alzheimer's Disease Imaging

The biomedical relevance of 1,4-naphthoquinone extends into neurology, specifically in the detection and study of Alzheimer's disease. Recent advancements have seen the synthesis of 41 novel 1,4-naphthoquinone derivatives, with 14 identified as antiamyloidogenic based on their ability to inhibit β-amyloid aggregation in vitro. Notably, compounds like 8-hydroxy-2-((3-methoxybenzyl)amino)naphthalene-1,4-dione and others have shown the ability to penetrate the blood-brain barrier, bind directly to β-amyloid aggregates, and enhance fluorescence upon interaction. These properties make them excellent candidates for staining and imaging β-amyloid plaques in brain sections of Alzheimer's disease models, suggesting 1,4-naphthoquinone derivatives as promising new scaffolds for the development of imaging agents aimed at the early detection of Alzheimer's pathology. ²

Reference

1. Aminin D, Polonik S. 1,4-Naphthoquinones: Some Biological Properties and Application. Chem Pharm Bull (Tokyo). 2020; 68(1): 46-57.

2. Naewoo NS. “Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains.” ACS Chemical Neuroscience. 2019; 10(6): 3031-3044.