Inactivation of Monoamine Oxidase B by Analogues of the Anticonvulsant Agent Milacemide (2-(n-Pentylamino)acetamide)

Kuniko Nishimura, Xingliang Lu, Richard B Silverman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Analogues of the anticonvulsant agent milacemide (1,2-(n-pentylamino)acetamide), in which the carboxamide group is changed to a nitrile (2), a carbethoxy group (3), a carboxylic acid (4), a cyanomethyl group (5), and a trifluoromethyl group (6), were synthesized and tested as substrates and inactivators of monoamine oxidase B (MAO B). The carboxylic acid was neither a substrate nor an inactivator. The trifluoromethyl compound was not soluble in buffer even when organic cosolvents were added, so it could not be tested. All of the other compounds were both substrates and time-dependent irreversible inactivators of MAO B. A plot of the logarithm of kcat/kinact (a measure of the efficiency of the inactivators) versus σI (Figure 1) shows a linear free energy relationship between the inactivator efficiency and the electron-withdrawing ability of the substituent. As the electron-withdrawing ability increases, the partition ratio decreases indicating that inactivation is becoming more efficient relative to substrate turnover to product. Milacemide was the least efficient of the compounds tested; the nitrile 2 was the most efficient.

Original languageEnglish (US)
Pages (from-to)446-448
Number of pages3
JournalJournal of Medicinal Chemistry
Volume36
Issue number4
DOIs
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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