Cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) metabolically activate polycyclic aromatic hydrocarbons (PAHs) to carcinogenic compounds. Aryl-morpholino triazenes inhibit CYP1A1 and CYP1B1 as a potential means to prevent cancer, but these compounds adopt a chair conformation which may not fit into the active site as well as a more planar molecule. Planar triazenes,1,3-bis(phenyl)triazene, 1,3-bis(4-bromophenyl)triazene, 1,3-bis(4-cyanophenyl)triazene and 1,3-bis(4-acetylphenyl)triazene, were synthesized from substituted aniline derivatives, such as aniline, 4-bromoaniline, 4-aminobenzonitrile, and 4-aminoacetophenone respectively, using 12 M HCl to generate a highly reactive diazonium ion. This was subsequently treated with NaNO2 which provided the third nitrogen in the triazene unit. These triazenes and respective starting materials were screened at 100 μM for their ability to inhibit CYP1A1 and CYP1B1. 1,3-bis(4-bromophenyl)triazene and 1,3-bis(4-cyanophenyl)triazene inhibited CYP1B1 to 45% and 36% of the uninhibited CYP1B1 respectively, while their aniline derivatives showed no inhibition of CYP1B1. 1,3-bis(4-acetylphenyl)triazene inhibited CYP1A1 to 40% of the uninhibited activity while its aniline derivative showed no inhibition of CYP1A1. Compounds that inhibit CYP1A1 and CYP1B1 will be analyzed for their IC50 values. The IC50 value of one compound, 1,3-bis(4-bromophenyl)triazene, has been determined to be 92 μM with respect to CYP1B1. This indicates linear triazenes are a new class of compounds that effectively inhibit CYP1A1 and CYP1B1 as a means to prevent cancer.

Planar aryl triazenes inhibit cytochrome P450 1A1 and 1B1 as a potential means to prevent cancer

253rd National Meeting (2017)

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