Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin, flufenamic acid, and related compounds have been recently identified as potent inhibitors of AKR1C3. We report that some other NSAIDs (diclofenac and naproxen) also inhibit AKR1C3, with the IC(50) values in the low micromolar range. In order to obtain more information about the structure-activity relationship and to identify new leads, a series of compounds designed on the basis of NSAIDs were synthesized and screened on AKR1C3. The most active compounds were 2-[(2,2-diphenylacetyl)amino]benzoic acid 4 (IC(50)=11microM) and 3-phenoxybenzoic acid 10 (IC(50)=0.68microM). These compounds represent promising starting points for the development of new anticancer agents.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
3-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
-
Aldo-Keto Reductase Family 1 Member C3
-
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
-
Anti-Inflammatory Agents, Non-Steroidal / chemistry
-
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
-
Antineoplastic Agents / chemistry*
-
Drug Design*
-
Enzyme Inhibitors / chemistry
-
Humans
-
Hydroxyprostaglandin Dehydrogenases / antagonists & inhibitors*
-
Molecular Structure
-
Tumor Cells, Cultured
Substances
-
Anti-Inflammatory Agents, Non-Steroidal
-
Antineoplastic Agents
-
Enzyme Inhibitors
-
3-Hydroxysteroid Dehydrogenases
-
Hydroxyprostaglandin Dehydrogenases
-
AKR1C3 protein, human
-
Aldo-Keto Reductase Family 1 Member C3