Title:In Vitro Screening of Some Heterocyclic Compounds Against Human ABHD6 and ABHD12 Hydrolases
Volume: 11
Issue: 7
Author(s): Agnieszka A. Kaczor, Antti Poso and Monika Pitucha
Affiliation:
Keywords:
ABHD6 inhibitors, ABHD12 inhibitors, In vitro screening.
Abstract: The ABHD6 and ABHD12 are newly discovered post-genomic proteins which act as 2-arachidonoylglycerol
hydrolases. Their physiological importance is largely unknown, however high expression of ABHD6 is attributed to some
forms of cancer. Only a few inhibitors are known for ABHD6 and ABHD12 enzymes. In search for novel inhibitors of
ABHD6 and ABHD12 hydrolases we tested a set of heterocyclic compounds which are lipophilic as required by the protein
binding pockets and possess suitable properties for being tested in the designed assay. The rationale of the study may
be summarized as follows: (1) almost all the compounds are relatively lipophilic; (2) some of the selected compounds exhibited
anticancer activity; (3) some of the selected compounds shared the same structural features with known ABHD6
inhibitors and (4) physicochemical properties of the compounds make it possible to test them in the in vitro assay against
ABHD6 and ABHD12 hydrolases. Although the studies did not make it possible to identify novel very potentABHD6 and
ABHD12 inhibitors, we have identified 6 weak inhibitors of ABHD6 and ABHD12 (non-selective) and inhibiting both
enzymes. The results obtained may be helpful for the design of novel active compounds.
