Unveiling the multifaceted biological activities of 1,3-benzodioxole derivatives

General Description

1,3-Benzodioxole derivatives have shown promising biological activities in various fields. They exhibit anti-tumor properties by inhibiting enzymes and promoting apoptosis, making them potential candidates for leukemia and tumor treatment. Additionally, these derivatives demonstrate anti-hyperlipidemia effects by reducing plasma lipids and improving liver function. They also exhibit antioxidative activity, with Hypecoumic acid showing moderate activity. These findings open new avenues for the development of therapeutic applications in medicine, food, and cosmetics. Further research is needed to uncover the underlying mechanisms and explore their full potential.

Figure 1. 1,3-Benzodioxole

Biological activities

Anti-tumor

1,3-Benzodioxole derivatives have shown promising biological activity in the treatment of leukemia and other tumors. In the field of cancer treatment, arsenicals have been commonly used but their side effects restrict their clinical application. To overcome this limitation, researchers drew inspiration from stiripentol, a medication used to treat epilepsy that has a good safety profile. Stiripentol works by inhibiting certain enzymes, thus prolonging the duration of co-administered drugs. Based on this concept, 1,3-benzodioxole derivatives, responsible for enzyme inhibition, were conjugated with arsenical precursors. The resulting fabricated arsenicals displayed slower elimination rates in mice, leading to a longer retention time in the bloodstream compared to the arsenical precursors alone. Moreover, these compounds exhibited enhanced anti-proliferative properties by inhibiting the thioredoxin system, inducing oxidative stress, and promoting apoptosis both in vitro and in vivo. Importantly, the fabricated arsenicals demonstrated the ability to reverse abnormal blood counts in tumor-bearing mice while effectively eliminating tumors without causing harm to other organs. This study showcases a well-designed strategy and promising pre-clinical application of 1,3-benzodioxole derivatives in the treatment of leukemia and other tumors. ¹

Anti-hyperlipidemia

A series of 1,3-benzodioxole-based fibrate derivatives were synthesized and evaluated for their biological activity. The compounds were tested on hyperlipidemia mice induced by Triton WR-1339. Among them, a compound exhibited superior anti-hyperlipidemia activity compared to other compounds and the positive control drug fenofibrate (FF). It showed remarkable reductions in plasma lipids, including triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterin (LDL-C), in hyperlipidemic mice induced by a high-fat diet (HFD). It also ameliorated the levels of hepatic transaminases (AST and ALT), particularly AST, indicating improved liver function. Histopathological examination further supported the finding that it reduced hepatic lipid accumulation. Moreover, the expression of PPAR-α, a protein involved in lipid metabolism, was up-regulated in the liver tissues of mice treated with compound 12. This suggests that compound 12 modulates lipid metabolism pathways. Additionally, compound 12 demonstrated significant antioxidant and anti-inflammatory activities, further reinforcing its potential as a hypolipidemic and hepatoprotective agent. In summary, 1,3-benzodioxole derivatives exhibited promising biological activities including anti-hyperlipidemia effects. In summary, the 1,3-benzodioxole derivative, compound 12, exhibited promising biological activities including anti-hyperlipidemia, hepatoprotection, antioxidant, and anti-inflammatory effects. These findings highlight its potential as a therapeutic agent for the treatment of lipid-related disorders. ²

Anti-oxidative

In a study, the researchers aimed to investigate the antioxidative activity of 1,3-benzodioxole derivatives found in the aerial parts of Hypecoum erectum. Several compounds were isolated and identified, including a new derivative called Hypecoumic acid as well as three known compounds: protopine, coptisine, and cryptopine. Furthermore, the antioxidative activity of all the compounds was evaluated using a DPPH-scavenging assay, an in vitro method for measuring antioxidant capacity. Among the compounds tested, compound 1 exhibited moderate antioxidative activity, with an IC50 value of 86.3 ± 0.2 μM. The IC50 value represents the concentration required to scavenge 50% of the free radicals generated by DPPH. This suggests that Hypecoumic acid has the potential to act as an antioxidant, which is important for its potential application in various fields, such as medicine, food, and cosmetics. Overall, this study provides valuable insights into the antioxidative activity of 1,3-benzodioxole derivatives, specifically highlighting the moderate antioxidative activity of Hypecoumic acid. Further research is warranted to explore the mechanisms underlying its antioxidative properties and to investigate its potential therapeutic applications. ³

Reference

1. Shi XM, She WY, Liu TT, Gao LX, Liu YJ, Liu Y. 1,3-Benzodioxole Derivatives Improve the Anti-Tumor Efficiency of Arsenicals. Int J Mol Sci. 2022 Jun 22;23(13):6930.

2. Xie YD, Xu YH, Liu JP, Wang B, Shi YH, Wang W, Wang XP, Sun M, Xu XY, Bian XL. 1,3-Benzodioxole-based fibrate derivatives as potential hypolipidemic and hepatoprotective agents. Bioorg Med Chem Lett. 2021 Jul 1;43:127898.

3. Xu N, Bao W, Xin J, Xiao H, Yu J, Xu L. A New 1,3-Benzodioxole Compound from Hypecoum erectum and Its Antioxidant Activity. Molecules. 2022 Oct 7;27(19):6657.