Design and Structure-Activity Relationships of Isothiocyanates as Potent and Selective N-Acylethanolamine-Hydrolyzing Acid Amidase Inhibitors

Michael S Malamas, Spiro Pavlopoulos, Shakiru O Alapafuja, Shrouq I Farah, Alexander Zvonok, Khadijah A Mohammad, Jay West, Nicholas Thomas Perry, Dimitrios N Pelekoudas, Girija Rajarshi, Christina Shields, Honrao Chandrashekhar, Jodi Wood, Alexandros Makriyannis. J Med Chem. 2021 May 13;64(9):5956-5972.

Laboratory studyHumansOther animals

Design

Laboratory study

Subjects

Human NAAA enzyme assays, plasma and microsomal stability tests; in vivo activity mentioned without species

Dose used in the study

Not applicable; palmitoylethanolamide was not given. The test compounds are isothiocyanate NAAA inhibitors

Duration

Not stated in the abstract

What was measured

Potency and selectivity of isothiocyanate inhibitors against human NAAA versus other serine hydrolases and cysteine peptidases; plasma and microsomal stability.

What the authors reported

The compounds produced were low nanomolar inhibitors of human NAAA with more than 100-fold selectivity over other enzymes, plasma half-life above 2 hours and microsomal half-life of about 15 to 30 minutes. NAAA breaks down palmitoylethanolamide. No disease-model results are given in the abstract.

Limits of this study

A medicinal chemistry and enzyme study; it cannot show effect in people or animals treated in practice. PEA itself was not tested. Funding and conflicts not stated in the abstract.

Source

PubMed 33900772 · doi:10.1021/acs.jmedchem.1c00076

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.