1,4-Benzoquinone: activities and toxicology

General Description

1,4-Benzoquinone is a chemical compound with diverse properties and potential applications. Derivatives of 1,4-Benzoquinone found in scorpion venom demonstrate antimicrobial effects, highlighting their therapeutic potential. Additionally, compounds containing the 1,4-benzoquinone subunit exhibit strong antitumor properties and cytotoxicity against tumor cells. Moreover, 1,4-Benzoquinone shows inhibitory effects on monoamine oxidase, particularly on MAO-A, which may have implications for therapeutic use in conditions related to monoamine regulation. However, it is important to note that 1,4-Benzoquinone is toxic and requires safe handling and storage to protect health and the environment.

Figure 1. 1,4-Benzoquinone

Activities

Antimicrobial effect

Two derivatives of 1,4-Benzoquinone with antimicrobial properties have been discovered in the venom of the scorpion Diplocentrus melici. They are a red compound (3,5-dimethoxy-2-(methylthio)cyclohexa-2,5-diene-1,4-dione) and a blue compound (5-methoxy-2,3-bis(methylthio)cyclohexa-2,5-diene-1,4-dione). The red benzoquinone showed effectiveness against Staphylococcus aureus, while the blue benzoquinone displayed activity against Mycobacterium tuberculosis, including a multidrug-resistant strain. Both compounds demonstrated antibacterial effects comparable to existing antibiotics targeting these pathogens. In addition to their antimicrobial properties, these benzoquinones also exhibited cytotoxicity towards neoplastic cell lines, suggesting their potential as lead compounds for the development of novel antimicrobial and anticancer drugs. Notably, the blue benzoquinone demonstrated efficacy in vivo using mouse models of multidrug-resistant tuberculosis infection. Treatment with the blue benzoquinone resulted in a significant reduction in pulmonary bacillary loads and tissue damage after a 2-month treatment period. Healthy mice tolerated the treatment well without any adverse side effects. Overall, these findings highlight the promising antimicrobial and anticancer potential of the derivatives of 1,4-Benzoquinone found in scorpion venom. Further research is needed to explore their therapeutic applications and develop effective treatments based on these compounds. ¹

Antitumor effect

The antitumor effect of 1,4-Benzoquinone can be summarized as follows. Compounds containing a 1,4-benzoquinone subunit have shown high biological activity and are used as medicinal agents and starting materials for semi-synthetic derivatives. Enediyne antibiotics such as dynemicin A, deoxydynemicin A, and uncilamicin contain the 1,4-benzoquinone fragment and exhibit strong antitumor properties. Researchers synthesized various derivatives with alkyl and enediyne fragments attached to the 1,4-benzoquinone moiety. These compounds were characterized and tested as antitumor agents. Depending on the specific type of 1,4-benzoquinone subunit and tumor cell line used, they demonstrated significant cytotoxic activity. Importantly, these synthesized derivatives comply with the Lipinski Rule of Five and have low permeability through the blood-brain barrier. Overall, the antitumor effect of 1,4-Benzoquinone is attributed to its ability to induce cytotoxicity in tumor cells, making it a promising candidate for cancer treatment studies. This research highlights the potential of utilizing 1,4-Benzoquinone-related compounds in the development of new antitumor drugs. ²

Inhibitor of monoamine oxidase

1,4-Benzoquinone has been studied for its inhibitory effect on type A and B monoamine oxidase (MAO-A and -B) in human brain synaptosomes. The results showed that MAO-A was significantly inhibited by 1,4-benzoquinone in a competitive manner with the substrate, kynuramine. In contrast, MAO-B exhibited less sensitivity to 1,4-benzoquinone as an inhibitor, and the inhibition was non-competitive with the substrate.The inhibition of MAO-A by 1,4-benzoquinone was confirmed using platelet mitochondria and clonal rat pheochromocytoma PC12h cells as alternative enzyme sources. Furthermore, the inhibition of MAO activity by 1,4-benzoquinone was reversible. It was demonstrated that the inhibited enzyme activity could be recovered through column chromatography on Sephadex G-25. Overall, these findings suggest that 1,4-Benzoquinone exhibits inhibitory effects on MAO-A, with potential implications for its therapeutic use in conditions related to monoamine regulation, such as depression and neurodegenerative disorders. ³

Toxicology

1,4-Benzoquinone is a chemical compound with toxic properties. Precautionary statements advise safe handling and storage. Dispose of properly, store locked up in a ventilated place, and collect spillage to prevent harm to aquatic life. In case of eye contact, rinse cautiously. Wear protective gear, avoid release to the environment, and use outdoors or in well-ventilated areas. Avoid eating, drinking, or smoking. Wash skin and hands thoroughly, and avoid inhaling dust or fumes. It is very toxic to aquatic life, may cause organ damage and respiratory/skin/eye irritation. Handle with care to protect health and the environment. ⁴

Reference

1. Carcamo-Noriega EN, Sathyamoorthi S, Banerjee S, Gnanamani E, Mendoza-Trujillo M, Mata-Espinosa D, Hernández-Pando R, Veytia-Bucheli JI, Possani LD, Zare RN. 1,4-Benzoquinone antimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom. Proc Natl Acad Sci U S A, 2019, 116(26):12642-12647.

2. Kadela-Tomanek M, B?benek E, Chrobak E, Latocha M, Boryczka S. Alkoxy and Enediyne Derivatives Containing 1,4-Benzoquinone Subunits-Synthesis and Antitumor Activity. Molecules, 2017, 22(3):447.

3. Naoi M, Nomura Y, Ishiki R, Suzuki H, Nagatsu T. 1,4-Benzoquinone as a new inhibitor of monoamine oxidase. Neurosci Lett, 1987, 77(2):215-220.

4. 1,4-Benzoquinone (para-quinone). IARC Monogr Eval Carcinog Risks Hum, 1999, 71 Pt 3(PT 3):1245-1250.

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