1,4- and 2,6-disubstituted amidoanthracene-9,10-dione derivatives as inhibitors of human telomerase

A number of 1,4- and 2,6-difunctionalized amidoanthracene-9, 10-diones have been prepared. We have examined their in vitro cytotoxicity in several tumor cell lines and their ability to inhibit the telomere-addition function of the human Telomerase enzyme together with their inhibition of the Taq polymerase Enzyme. Compounds with -(CH2)2- side chains terminating in basic groups such as piperidine show inhibition of Telomerase at telIC50 levels of 4-11 microM. These are thus among the most potent nonnucleoside Telomerase inhibitors reported to date. Cytotoxicity levels in human tumor cell lines were at comparable levels for several compounds. Implications for amidoanthracene-9,10-dione Telomerase inhibitors as potential Anticancer agents are discussed.