In vitro and in vivo imaging of Phase I xenobiotic-metabolizing enzymes

Real-time fluorescent monitoring of phase I xenobiotic-metabolizing enzymes

“…However, their specicity in distinguishing from butyrylcholinesterase (BChE) improved, with probe 27 demonstrating the highest level of specicity and uorescence at 460 nm. 10 Chemosensor probe 27 targeted both isoforms, CE1 and CE2, with the pivaloyl group serving as the recognition site, providing superior spec-icity compared to other small molecule probes with an acetyl group as the recognition site (Table 1). The pivaloyl group also imparted steric hindrance to other esterases, including butyrylcholinesterase (BChE) and acetylcholinesterase (AChE).…”

“…1. 10 Phase I metabolism entails the modication and biotransformation of xenobiotics and toxic substances by introducing or unmasking polar groups such as -SH, -OH, -OR, and -NH 2 into the parent compound. This intricate biotransformation process is orchestrated by a complex system of enzymes.…”

“…These enzymes catalyze the conjugation of Phase I reaction products with compounds such as glucuronic acid, glutathione, and sulfate. 10,12 Phase III, termed the extrusion phase, further enhances the polarity of these metabolites through hydroxylation, rendering them more water-soluble. Subsequently, these hydroxylated metabolites are primed for excretion by the liver or kidneys, as depicted in Fig.…”

“…9,14 Phase I enzymes have garnered attention in the development of enzyme-directed uorescence chemosensors, owing to their inclusion of pharmacologically signicant enzymes such as esterase, cytochrome P450 family, monoamine oxidase, nitroreductase, aldehyde dehydrogenase, and glycosidase. 10,15 These enzymes actively participate in the metabolism and activation of numerous prodrugs, with their overexpression in cancer cells marking them as potential biomarkers for early-stage cancer diagnosis and monitoring therapeutic efficacy of cancer drugs. [16][17][18][19] Anticipating a surge in cancer cases, the World Health Organization predicts 24 million new cases and 14.4 million annual deaths by 2035.…”

“…This demand arises from critical research domains including theranostics, targeted drug design, and the visual detection of drug resistance. 10 This comprehensive review delves into recent advancements in uorescent chemosensors, focusing on their diagnostic applications for Phase I enzymes based on enzymatic oxidative, reductive, and hydrolytic reactions. The review highlights in vitro and in vivo diagnostic uses of small molecule-based uorescent chemosensors for Phase I xenobiotic metabolizing enzymes, exploring how xenobiotic metabolism induces changes in the uorescence of small molecules through structural modications.…”