Pentafluorobenzaldehyde: A new potent inhibitor of aldehyde dehydrogenase isoenzymes

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

Pentafluorobenzaldehyde: A new potent inhibitor of aldehyde dehydrogenase isoenzymes

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

Medicine - General Internal Medicine

Research output: Contribution to journal › Article › peer-review

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 K_m and low V_max). Therefore, compound 1 represents novel mechanism than that of disulfiram in inhibiting ALDH.

Original language	English (US)
Pages (from-to)	P40
Journal	Clinical pharmacology and therapeutics
Volume	69
Issue number	2
State	Published - Dec 1 2001

Find It

Find It at U of M Libraries

Cite this

@article{388f3bbe2e16400e86b444f9d3583cfc,

title = "Pentafluorobenzaldehyde: A new potent inhibitor of aldehyde dehydrogenase isoenzymes",

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.",

author = "Macomber, \{D. W.\} and Mays, \{D. C.\} and Susan Buckheister and Lipsky, \{J. J.\}",

year = "2001",

month = dec,

day = "1",

language = "English (US)",

volume = "69",

pages = "P40",

journal = "Clinical pharmacology and therapeutics",

issn = "0009-9236",

publisher = "Wiley-Blackwell",

number = "2",

}

TY - JOUR

T1 - Pentafluorobenzaldehyde

T2 - A new potent inhibitor of aldehyde dehydrogenase isoenzymes

AU - Macomber, D. W.

AU - Mays, D. C.

AU - Buckheister, Susan

AU - Lipsky, J. J.

PY - 2001/12/1

Y1 - 2001/12/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/33748964811

UR - https://www.scopus.com/pages/publications/33748964811#tab=citedBy

M3 - Article

AN - SCOPUS:33748964811

SN - 0009-9236

VL - 69

SP - P40

JO - Clinical pharmacology and therapeutics

JF - Clinical pharmacology and therapeutics

IS - 2

ER -

Pentafluorobenzaldehyde: A new potent inhibitor of aldehyde dehydrogenase isoenzymes

Abstract

Find It

Other files and links

Fingerprint

Cite this