Novel advances in biotransformation and bioactivation research—2019 year in review

Abstract

This annual review is the sixth of its kind since 2016 (see references). Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation and bioactivation. These fields are constantly evolving with new molecular structures and discoveries of corresponding pathways for metabolism that impact relevant drug development with respect to efficacy and safety. Based on the selected articles, we created three sections: (1) drug design, (2) metabolites and drug metabolizing enzymes, and (3) bioactivation and safety (Table 1). Unlike in years past, more biotransformation experts have joined and contributed to this effort while striving to maintain a balance of authors from academic and industry settings.

Transcriptomics and metabolomics reveal the role of CYP1A2 in psoralen/isopsoralen‐induced metabolic activation and hepatotoxicity

“…It is cautioned that potential side effects of interactions between psoralen or isopsoralen with CYP1A2 Furan-containing compounds are often suspected to bring about hepatotoxicity through the formation of reactive intermediates by metabolic activation of CYP450, which subsequently bind to intracellular GSH, DNA, proteins, etc., and induce cytotoxicity (Peterson, 2013;Wang et al, 2021). This theory has undergone some practices (Khojasteh et al, 2020;Wang et al, 2021), for example, furanoid diterpene lactones of disobulbin A, B, C, and F isolated from Dioscorea bulbifera L. were metabolized by CYP3A to cis-enedial intermediates, which were responsible for the observed hepatotoxicity (Li et al, 2016;Wu et al, 2020). In addition, the furan rings of furancontaining components such as rutaevin (Liu, Li, et al, 2020;, columbin (Pei et al, 2020), nomilin (Zhang et al, 2020), etc.…”