Literature

Abstract

A novel series of benzo[a]phenazin derivatives bearing alkylamino side chains were designed, synthesized and evaluated for their topoisomerases inhibitory activity as well as cytotoxicity against four human cancer cell lines (HL-60, K-562, HeLa, and A549). These compounds were found to be dual inhibitors of topoisomerase (Topo) I and Topo II, and exhibited excellent antiproliferative activity, in particular against HL-60 cells with submicromolar IC50 values. Further mechanistic studies showed that this class of compounds acted as Topo I poisons by stabilizing the Topo I-DNA cleavage complexes and Topo II catalytic inhibitors by inhibiting the ATPase activity of hTopo II. Molecular docking studies revealed the binding modes of these compounds for Topo I and Topo II.

DOI： 10.1016/j.ejmech.2015.01.024

Design, synthesis and biological evaluation of novel 7-alkylamino substituted benzo[a]phenazin derivatives as dual topoisomerase I/II inhibitors

European Journal of Medicinal Chemistry 2015.0

Synthesis and Mechanism Studies of 1,3-Benzoazolyl Substituted Pyrrolo[2,3-b]pyrazine Derivatives as Nonintercalative Topoisomerase II Catalytic Inhibitors

Journal of Medicinal Chemistry 2016.0

Novel Angular Benzophenazines: Dual Topoisomerase I and Topoisomerase II Inhibitors as Potential Anticancer Agents

Journal of Medicinal Chemistry 2002.0

Design, synthesis and biological evaluation of benzimidazole–rhodanine conjugates as potent topoisomerase II inhibitors

MedChemComm 2018.0

Rational design, synthesis, and evaluation of novel 2,4-Chloro- and Hydroxy-Substituted diphenyl Benzofuro[3,2-b]Pyridines: Non-intercalative catalytic topoisomerase I and II dual inhibitor

European Journal of Medicinal Chemistry 2017.0

Synthesis and biological evaluation of N -(carbobenzyloxy)- l -phenylalanine and N -(carbobenzyloxy)- l -aspartic acid- β -benzyl ester derivatives as potent topoisomerase IIα inhibitors