Affiliation: University of Eastern Finland, School of Pharmacy, Department of Pharmaceutical Chemistry, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland.
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.