Fluorescent probes for the detection and imaging of Cytochrome P450

摘要

Cytochrome P450 (CYP) enzymes are haem-containing proteins which are mainly involved in the oxidative metabolism of various chemicals. CYP enzymes can be affected by co-administrated drugs, environmental factors, disease states and genetic polymorphism, leading to differing degrees of individual variability of CYP activity which can induce the adverse effect of drugs or result in the failure of a drug therapy with varying severity. In this arena, fluorescent probes can serve as useful molecular tools to selectively detect CYP activity, facilitated by their intrinsic sensitivity and capacity for rapid, real-time and in situ monitoring as well as high-throughput screening. Therefore, the design of enzymatic activity reporters serving as the CYP subtype-specific probes, has stimulated widespread interest. This review covers the design principles for probes and systemically summarizes recent advances in the development of fluorescent probes for CYP isoforms including CYP1A, CYP1A1, CYP2C9, CYP2D6, CYP2J2, CYP3A, CYP3A4, CYP3A7, CYP4A11, CYP4F12 and CYP4F3B, and also probes for detecting the reduction ability of CYP, then categorizes these molecular tools according to the detection strategy or interaction models for the key CYP isoforms, such as dealkylation, hydroxylation or reduction reactions. In addition, challenges and future perspectives in the development of selective and sensitive fluorescent probes of CYP are discussed. (C) 2020 Elsevier B.V. All rights reserved.