Studies on anthracenes. 1. Human telomerase inhibition and lipid peroxidation of 9-acyloxy 1,5-dichloroanthracene derivatives

The synthetically useful approaches to 9-acyloxy 1,5-dichloroanthracene der ivatives are reported. The system selectively reduces the carbonyl group fl anked by the peri substituents of the anthracenediones to give the correspo nding 1,5-dichloro-9(10H)-anthracenone. Simple regioselective acylation of anthracenone is applied with appropriate acyl chlorides in CH2Cl2 with cata lytic amount of pyridine to give the novel 9-acyloxy 1,5-dichloroanthracene derivatives. Considerable interest has developed in the mechanism of how a nthracenone achieves this desirable selectivity. In an attempt to understan d the mechanism of this reaction, solid-state structures of anthracene deri vatives have been obtained. In addition, the inhibition of lipid peroxidati on in model membranes was determined as was their ability to inhibit the te lomere-addition function of the human telomerase enzyme together with their inhibition of the Taq polymerase enzyme. In contrast to (+)-alpha -tocophe rol, 3b, 3c, 3d, 3g, and 3i do not enhance lipid peroxidation in model memb ranes. Implications for 9-acyloxy 1,5-dichloroanthracene analogues as poten tial anticancer agents are discussed.