Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

Abstract

Furan-containing compounds are abundant in nature, of which many but not all have been found to be hepatotoxic and carcinogenic. The furan ring present in the chemical structures may be one of the domineering factors to bring about the toxic response resulting from the generation of reactive epoxide or cis-enedial intermediates which are of the potential to react with biomacromolecules. This review sets out to explore the relationship between the metabolic activation and hepatotoxicity of furan-containing compounds on the strength of scientific reports on several typical alkylated furans, synthetic pharmaceuticals and components extracted from herbal medicines. The pharmacological activities as well as concrete evidence of their liver injuries are described, and the potential toxic mechanisms were discussed partly based on our previous work. Efforts were made to understand the development of liver injury and seek solutions to prevention and interference of the adverse effects.

Discovery of Pyridinone Derivatives as Potent, Selective, and Orally Bioavailable Adenosine A2A Receptor Antagonists for Cancer Immunotherapy

“…As noticed in literature, the left-hand side (LHS) methylfuran ring in compound 1 seems an often-seen structure moiety for A 2A R antagonists. However, the furan moiety may bring about potential toxicity due to the generation of reactive epoxide or cis -enedial intermediates, which have the potential to react with biomacromolecules . Therefore, we tried first to remove the methylfuran ring and designed a phenyl derivative 2 .…”

“…However, the furan moiety may bring about potential toxicity due to the generation of reactive epoxide or cis-enedial intermediates, which have the potential to react with biomacromolecules. 24 Therefore, we tried first to remove the methylfuran ring and designed a phenyl derivative 2. It turned out that compound 2 showed higher inhibition rate (65.0% inhibition at the concentration of 10 μM) against A 2A R than compound 1 (Table 1), but compound 2 had a short half-life (t 1/2 = 22.8 min) in mouse liver microsome (MLM) (Table S1).…”

“…When comparing the sulfonamide group (30) with the methylsulfonyl group (31), the activity of the latter showed an increase of about 3 times relative to that of the former. However, in general, most electron-withdrawing substituents did not make obvious improvement compared with the methoxycarbonyl group (24). In addition, we designed compounds to explore the effect of electron-donating polar and non-polar substituents on activity.…”

Novel Sulfonylurea-Based NLRP3 Inflammasome Inhibitor for Efficient Treatment of Nonalcoholic Steatohepatitis, Endotoxic Shock, and Colitis

“…In this study, we designed and synthesized a series of NLRP3 inflammasome inhibitors, building upon the foundation of MCC950 and focusing on the optimization of its furan moiety in order to improve druggability. , We evaluated the safety profile of the representative compound ( N14 ) using virtual software and cell-based experiments and validated its selectivity in inhibition of the NLRP3 inflammasome. We conducted pharmacokinetic and in vivo efficacy studies in animal models of NASH, colitis, and lethal endotoxic shock.…”

Ru(ii)-catalyzed synthesis of poly-substituted furans via intermolecular oxidative annulation reaction of ethyl 3-oxo-3-phenylpropanoates with aryl alkynes/heteroaryl alkynes

“…Polyfunctionalized furans constitute an important class of five-membered O-heterocycles with widespread applications. 1 Furans are extremely important heterocyclic compounds (Fig. 1) 2–5 and worthy of attention as they exhibit a wide range of biological activities.…”