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Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde

The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short chain 2-alkenal formed during lipid peroxidation. We here report the chemistry of acrolein-trapping by hydralazine, and show that together with its structural analogue dihydralazine, it also readily traps...

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Published in:	Organic & biomolecular chemistry 2004-09, Vol.2 (18), p.2578
Main Authors:	Kaminskas, Lisa M, Pyke, Simon M, Burcham, Philip C
Format:	Article
Language:	English
Subjects:	Acrolein - chemistry Acrolein - toxicity Aldehydes - chemistry Aldehydes - toxicity Animals Cells, Cultured Chromatography, High Pressure Liquid Culture Media Hepatocytes - drug effects Hepatocytes - metabolism Hydralazine - chemistry Hydralazine - pharmacology Kinetics Lipid Peroxidation Mice Molecular Structure
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container_title	Organic & biomolecular chemistry
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creator	Kaminskas, Lisa M Pyke, Simon M Burcham, Philip C
description	The nucleophilic drug hydralazine strongly inhibits cell toxicity mediated by acrolein, a short chain 2-alkenal formed during lipid peroxidation. We here report the chemistry of acrolein-trapping by hydralazine, and show that together with its structural analogue dihydralazine, it also readily traps crotonaldehyde. Isolable reaction products included (1E)-acrylaldehyde phthalazin-1-ylhydrazone (E-APH), (1Z)-acrylaldehyde phthalazin-1-ylhydrazone (Z-APH), (1E,2E)-but-2-enal phthalazin-1-ylhydrazone (E-BPH) and (1Z,2E)-but-2-enal phthalazin-1-ylhydrazone (Z-BPH). Concentration-dependent formation of (1E)-acrylaldehyde phthalazin-1-ylhydrazone was observed in the culture media of cells co-exposed to hydralazine and the acrolein precursor allyl alcohol. These aldehyde-sequestering properties of hydrazinophthalazine drugs may contribute to the protection they provide against 2-alkenal-mediated toxicity.
doi_str_mv	10.1039/B408796H
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source	Royal Society of Chemistry: Jisc Collections: Journals Archive 1841-2007 (2019-2023)
subjects	Acrolein - chemistry Acrolein - toxicity Aldehydes - chemistry Aldehydes - toxicity Animals Cells, Cultured Chromatography, High Pressure Liquid Culture Media Hepatocytes - drug effects Hepatocytes - metabolism Hydralazine - chemistry Hydralazine - pharmacology Kinetics Lipid Peroxidation Mice Molecular Structure
title	Reactivity of hydrazinophthalazine drugs with the lipid peroxidation products acrolein and crotonaldehyde
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