Chemical Identity of Interaction of Protein with Reactive Metabolite of Diosbulbin B In Vitro and In Vivo

Wang, Kai; Lin, Dongju; Guo, Xiuping; Huang, Wenlin; Peng, Ying; Zheng, Jiang

doi:10.3390/toxins9080249

Cited by 23 publications

(17 citation statements)

References 29 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protein adduction was time-and dose-dependent in DSB-treated mice. Pretreatment of animals with KTC decreased the crosslink, while pretreatment with dexamethasone (DEX) or buthionine sulfoximine (BSO, an inhibitor of GSH biosynthesis) provided the opposite result, further illustrating the vital role of the metabolic activation in the reaction between DSB and proteins (Wang et al, 2017). This makes us to speculate that modification of vital cellular proteins by DSB-derived cisenedial (DDE) would disturb the normal functions and trigger liver injury.…”

Section: Diosbulbin Bmentioning

confidence: 99%

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

2022

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Diosbulbin Bmentioning

confidence: 99%

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Depending on the protein microenvironment, DMPCs can develop from other amino acid residues of proteins, such as lysine, 74 tyrosine, 68 histidine, 64 and serine 25 (Table 1). For example, sulfonyl fluoride as an electrophile targets lysine and tyrosine, 60,67 furan targets lysine and cysteine, 29,57 epoxide targets methionine and cysteine, 25,45 and α,βunsaturated carbonyl targets histidine and cysteine, 42,64 and diphenyl phosphonate, β-lactam, and β-lactone target serine (Table 1). [69][70][71] In addition, the investigation of targeting aspartates and glutamates also achieved initial success.…”

Section: Modified Amino Acid Residues In Proteinsmentioning

confidence: 99%

Dual roles of drug or its metabolite−protein conjugate: Cutting‐edge strategy of drug discovery using shotgun proteomics

Gong

Chen

Sun

et al. 2022

Medicinal Research Reviews

View full text Add to dashboard Cite

Many drugs can bind directly to proteins or be bioactivated by metabolizing enzymes to form reactive metabolites (RMs) that rapidly bind to proteins to form drug−protein conjugates or metabolite−protein conjugates (DMPCs). The close relationship between DMPCs and idiosyncratic adverse drug reactions (IADRs) has been recognized; drug discovery teams tend to avoid covalent interactions in drug discovery projects. Covalent interactions in DMPCs can provide high potency and long action duration and conquer the intractable targets, inspiring drug design, and development. This forms the dual role feature of DMPCs. Understanding the functional implications of DMPCs in IADR control and therapeutic applications requires precise identification of these conjugates from complex biological samples. While classical biochemical methods have contributed significantly to DMPC detection in the past decades, the low abundance and low coverage of DMPCs have become a bottleneck in this field. An emerging transformation toward shotgun proteomics is on the rise. The evolving shotgun proteomics techniques offer improved reproducibility, throughput, specificity, operability, and standardization. Here, we review recent progress in the systematic discovery of DMPCs using shotgun proteomics. Furthermore, the applications of shotgun proteomics supporting drug development, toxicity mechanism investigation, and drug repurposing processes are also reviewed and prospected.

show abstract

“…The sensitive mass spectrometry strategy has been built to detect furans reactive metabolites plus GSH conjugates, such as neutral loss scanning of 290.0573 Da in the positive ionization mode, and precursor ion scanning of m/z 143.0462 + in the negative ionization mode ( Wang et al, 2014b ). Moreover, cis-enedial-protein adduct can be analyzed, cysteine (Cys) and lysine (Lys) residue of protein could be easily captured by cis-enedial to form three kinds of protein abnormal modification, through Cys adduction, Schiff’s base, or Cys/Lys crosslink ( Wang et al, 2017a ), respectively. In addition, the protein adductions of reactive metabolites of furans were determinated as Cys-and Lys-based protein adductions with the reactive metabolites ( Wang et al, 2015 ).…”

Section: Cyp450s Mediated Metabolic Activation Of Natural Products Leading To Toxicitymentioning

confidence: 99%

Metabolic Activation of the Toxic Natural Products From Herbal and Dietary Supplements Leading to Toxicities

Wang

Xia

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Currently, herbal and dietary supplements have been widely applied to prevent and treat various diseases. However, the potential toxicities and adverse reactions of herbal and dietary supplements have been increasingly reported, and have gradually attracted widespread attention from clinical pharmacists and physicians. Metabolic activation of specific natural products from herbal and dietary supplements is mediated by hepatic cytochrome P450 or intestinal bacteria, and generates chemical reactive/toxic metabolites that bind to cellular reduced glutathione or macromolecules, and form reactive metabolites-glutathione/protein/DNA adducts, and these protein/DNA adducts can result in toxicities. The present review focuses on the relation between metabolic activation and toxicities of natural products, and provides updated, comprehensive and critical comment on the toxic mechanisms of reactive metabolites. The key inductive role of metabolic activation in toxicity is highlighted, and frequently toxic functional groups of toxic natural products were summarized. The biotransformation of drug cytochrome P450 or intestinal bacteria involved in metabolic activation were clarified, the reactive metabolites-protein adducts were selected as biomarkers for predicting toxicity. And finally, further perspectives between metabolic activation and toxicities of natural products from herbal and dietary supplements are discussed, to provide a reference for the reasonable and safe usage of herbal and dietary supplements.

show abstract

Chemical Identity of Interaction of Protein with Reactive Metabolite of Diosbulbin B In Vitro and In Vivo

Cited by 23 publications

References 29 publications

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

Metabolic Activation and Hepatotoxicity of Furan-Containing Compounds

Dual roles of drug or its metabolite−protein conjugate: Cutting‐edge strategy of drug discovery using shotgun proteomics

Metabolic Activation of the Toxic Natural Products From Herbal and Dietary Supplements Leading to Toxicities

Contact Info

Product

Resources

About