Aryl morpholino triazenes inhibit cytochrome P450 1A1 and 1B1.
Many cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) inhibitors, such as resveratrol, have planar, hydrophobic, aromatic rings in their structure and exhibit anti-cancer activity. Aryl morpholino triazenes have similar structural features and in addition contain a triazene unit consisting of three consecutive, conjugated nitrogen atoms. Several aryl morpholino triazenes, including 4-[(E)-2-(3,4,5-trimethoxyphenyl)diazenyl]-morpholine (2), were prepared from a reaction involving morpholine and a diazonium ion produced from different aniline derivatives, such as 3,4,5-trimethoxyaniline. The aryl morpholino triazenes were then screened at 100μM for their ability to inhibit CYP1A1 and CYP1B1 using ethoxyresorufin as the substrate. Triazenes that inhibited the enzymes to less than 80% of the uninhibited enzyme activity were assayed to determine their IC50 value. Compound 2 was the only triazene to inhibit both CYP1A1 and CYP1B1 to the same degree as resveratrol with IC50 values of 10μM and 18μM, respectively. Compounds 3 and 6 selectively inhibited CYP1B1 over CYP1A1 with IC values of 2μM and 7μM, respectively. Thus, aryl morpholino triazenes are a new class of compounds that can inhibit CYP1A1 and CYP1B1 and potentially prevent cancer.
Department of Chemistry, Whittier College, Whittier, CA 90608, United States.
Daniel
D
Lee
Department of Chemistry, Whittier College, Whittier, CA 90608, United States.
Pedro
P
Perez
Department of Chemistry, Whittier College, Whittier, CA 90608, United States.
William
W
Jackson
Department of Chemistry, Whittier College, Whittier, CA 90608, United States.
Taylor
T
Chin
Department of Chemistry, Whittier College, Whittier, CA 90608, United States.
Michael
M
Galbreath
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, United States.
Frank R
FR
Fronczek
Department of Chemistry, Whittier College, Whittier, CA 90608, United States.
Ralph
R
Isovitsch
Department of Chemistry, Whittier College, Whittier, CA 90608, United States. Electronic address: diimoto@whittier.edu.
Devin S
DS
Iimoto
D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D060172:Morpholinos / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014226:Triazenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D060172:Morpholinos; D014226:Triazenes; C569463:CYP1A1 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
Cancer; Cytochrome P450 1A1; Cytochrome P450 1B1; Inhibition; Synthesis; Triazenes