ALPHA-HYDROXYTROPOLONES - A NEW CLASS OF POTENT INHIBITORS OF INOSITOL MONOPHOSPHATASE AND OTHER BIMETALLIC ENZYMES

Mono- and polyhydroxytropolones are potent competitive inhibitors of i nositol monophosphatase. Modeling studies indicate that this inhibitio n occurs most probably through a novel mode of action involving the ch elation of the two magnesium ions in the active site. This is consiste nt with experimental data. Inhibition occurs when at least three oxyge n atoms are present on the seven-membered ring, and only if they are c ontiguous to one another. Ln addition, those oxygens should not be pro tected. The corresponding six-membered rings showed no activity. Other bimetallic enzymes such as alkaline phosphatase (APase) or dopamine b eta-monooxygenase (DBM) are also inhibited (in a competitive or uncomp etitive manner) by hydroxytropolones.