Add time:08/11/2019         Source:sciencedirect.com

As part of a routine screening assay, benzaldehyde was found to inhibit 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism. Consequently, the effects of benzaldehyde and several structurally related compounds on NNK metabolism were examined in murine hepatic and pulmonary microsomes. All test compounds inhibited formation of the metabolites 4-oxo-4-(3-pyridyl)butyric acid (OPBA), 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in hepatic microsomes and inhibited formation of 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK N-oxide), HPB, and NNAL in pulmonary microsomes. m-Anisaldehyde was the most potent inhibitor, and p-hydroxybenzaldehyde and syringaldehyde were less potent than benzaldehyde and vanillin in inhibiting the formation of OPBA and HPB, NNK metabolites that reflect metabolic activation (α-hydroxylation). Vanillin was essentially as potent as benzaldehyde. The mechanism of inhibition exhibited by these compounds appears to be competitive in nature. The ability of these compounds to inhibit NNK activation suggests that these compounds may be effective blocking agents (anti-initiating agents) for NNK lung tumorigenesis.

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