Aryl morpholino triazenes inhibit cytochrome P450 1A1 and 1B1

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• 作者：Daniel Lee^a ; Pedro Perez^a ; William Jackson^a ; Taylor Chin^a ; ^&dagger ; ; Michael Galbreath^a ; Frank R. Fronczek^b ; Ralph Isovitsch^a ; Devin S. Iimoto^a ; ^{diimoto@whittier.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Triazenes ; Cytochrome P450 1A1 ; Cytochrome P450 1B1 ; Cancer ; Inhibition ; Synthesis
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 July 2016
• 年：2016
• 卷：26
• 期：14
• 页码：3243-3247
• 全文大小：449 K

文摘

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 100 μM 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 10 μM and 18 μM, respectively. Compounds 3 and 6 selectively inhibited CYP1B1 over CYP1A1 with IC values of 2 μM and 7 μM, respectively. Thus, aryl morpholino triazenes are a new class of compounds that can inhibit CYP1A1 and CYP1B1 and potentially prevent cancer.