Pentafluorobenzaldehyde: A new potent inhibitor of aldehyde dehydrogenase isoenzymes

D. W. Macomber, D. C. Mays, Susan Buckheister, J. J. Lipsky

Research output: Contribution to journalArticle

Abstract

Pentafluorobenzaldehyde (1) has been found to be a potent inhibitor of both Class 1 and 2 aldehyde dehydrogenase isoenzymes, which are major enzymes involved in ethanol metabolism. Compound 1 inhibits human recombinant cytosolic ALDH1 activity towards acetaldehyde/NAD+ with an IC50 value of 1.6 μM, whereas human recombinant mitochondrial ALDH2 is inhibited similarly with an IC50 of 1 μM. By comparison, previous work from our laboratory (Biochemistry 36, 13748-13754, 1997) has shown, under similar conditions, the IC50 values for disulfiram were 0.15 and 1.45 μM, respectively. The inhibitory activity of 1 towards ALDH1 and ALDH2 using different aldehydes/NAD+ is proposed to occur by an alternative substrate process in which 1 forms a tight-binding complex with the ALDH isoenzymes with subsequent slow turnover (i.e. low Km and low Vmax). Therefore, compound 1 represents novel mechanism than that of disulfiram in inhibiting ALDH.

Original languageEnglish (US)
Pages (from-to)P40
JournalClinical pharmacology and therapeutics
Volume69
Issue number2
StatePublished - Dec 1 2001

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Aldehyde Dehydrogenase
Isoenzymes
Inhibitory Concentration 50
Disulfiram
NAD
Acetaldehyde
Aldehydes
Biochemistry
Ethanol
Enzymes
aldehyde dehydrogenase 1
pentafluorobenzaldehyde

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Pentafluorobenzaldehyde : A new potent inhibitor of aldehyde dehydrogenase isoenzymes. / Macomber, D. W.; Mays, D. C.; Buckheister, Susan; Lipsky, J. J.

In: Clinical pharmacology and therapeutics, Vol. 69, No. 2, 01.12.2001, p. P40.

Research output: Contribution to journalArticle

Macomber, D. W. ; Mays, D. C. ; Buckheister, Susan ; Lipsky, J. J. / Pentafluorobenzaldehyde : A new potent inhibitor of aldehyde dehydrogenase isoenzymes. In: Clinical pharmacology and therapeutics. 2001 ; Vol. 69, No. 2. pp. P40.
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