Perry P J, Gowan S M, Reszka A P, Polucci P, Jenkins T C, Kelland L R, Neidle S
Cancer Research Campaign Biomolecular Structure Unit and Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
J Med Chem. 1998 Aug 13;41(17):3253-60. doi: 10.1021/jm9801105.
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.
已经制备了多种1,4 - 和2,6 - 双官能化的氨基蒽-9,10 - 二酮。我们研究了它们在几种肿瘤细胞系中的体外细胞毒性，以及它们抑制人端粒酶端粒添加功能的能力，同时还研究了它们对Taq聚合酶的抑制作用。具有以碱性基团（如哌啶）结尾的-(CH2)2-侧链的化合物在4 - 11 microM的端粒酶IC50水平下显示出对端粒酶的抑制作用。因此，这些是迄今为止报道的最有效的非核苷类端粒酶抑制剂。几种化合物在人肿瘤细胞系中的细胞毒性水平相当。讨论了氨基蒽-9,10 - 二酮端粒酶抑制剂作为潜在抗癌剂的意义。
