Covalent conjugates of topoisomerase I and topoisomerase II inhibitors

摘要

The present invention provides covalent conjugates of topoisomerase I and topoisomerase II inhibitors. Such compounds have a structure according to formula I:; $PTEXTPDATT/PDATHILSBPDATI/PDAT/SB/HILPDAT\—L\—T/PDATHILSBPDATII/PDAT/SB/HILPDAT\ \ (I)/PDAT/PTEXT$ ;wherein:;T_I is a topoisomerase I inhibitor such as a camptothecin group;;T_II is a topoisomerase II inhibitor such as an amsacrine, ellipticine, epipodophyllotoxin, or anthracycline antibiotic group; and;L is a linking group.;The compounds are useful for inhibiting topoisomerase I and II enzymes, for promoting cellular differentiation, and for treating cancer.