7-Alkoxyquinolines: new fluorescent substrates for cytochrome P450 monooxygenases

Biochem Pharmacol. 1990 Oct 1;40(7):1645-55. doi: 10.1016/0006-2952(90)90467-y.


A series of 7-alkoxyquinolines was synthesized and tested as substrates with hepatic microsomes prepared from male Wistar rats. Microsomal O-dealkylation rates and kinetic constants were determined for the 7-alkoxyquinolines with microsomes from control, 3-methylcholanthrene (MC)-pretreated, and phenobarbitone (PB)-pretreated rats. Structure-activity relationship studies indicated that the 7-benzyloxyquinoline was the most rapidly metabolized substrate for control microsomes and those from PB-pretreated rats, whereas the 7-ethoxy- and 7-propoxyquinolines were O-dealkylated more rapidly by microsomes of MC-pretreated animals. Differences in activities occurred in Vmax and apparent Km values; however, there does not appear to be a correlation between these two values for the different quinoline substrates. Apparent Km and Vmax values for the 7-alkoxyquinolines were: control microsomes, Km = 71-773 microM, Vmax = 0.37-8.4 nmol 7-quinolinol/min/mg protein; MC microsomes, Km = 0.5-14 microM, Vmax = 0.29-2.7 nmol 7-quinolinol/min/mg protein; PB microsomes, Km = 2.8-46 microM, Vmax = 0.9-12 nmol 7-quinolinol/min/mg protein. All of the quinoline substrates gave Type I binding spectra with control and MC microsomes. With PB microsomes, Type I. Reverse Type I, and a mixture of the two types of binding spectra were observed. Comparisons of the structure-activity relationships, levels of induction, and kinetic constants were made with 7-alkoxycoumarin and 7-alkoxyphenoxazone analogs. In addition, three new coumarin substrates (7-pentoxy-, 7-hexoxy-, and 7-benzyloxycoumarin) are described.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coumarins / chemical synthesis
  • Coumarins / metabolism
  • Cytochrome P-450 Enzyme System / metabolism*
  • Enzyme Activation
  • Hydrogen-Ion Concentration
  • Kinetics
  • Male
  • Microsomes, Liver / metabolism
  • Oxazines / chemical synthesis
  • Oxazines / metabolism
  • Quinolines / chemical synthesis*
  • Quinolines / metabolism
  • Rats
  • Rats, Inbred Strains
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship
  • Substrate Specificity


  • Coumarins
  • Oxazines
  • Quinolines
  • 7-hexoxyquinoline
  • 7-benzyloxyquinoline
  • 7-methoxyquinoline
  • Cytochrome P-450 Enzyme System