Quinoline anticancer agents active on DNA and DNA-interacting proteins: From classical to emerging therapeutic targets

Y Quinoline is one of the most important and versatile nitrogen heterocycles embodied in several biologically active molecules. Within the numerous quinolines developed as antiproliferative agents, this review is focused on compounds interfering with DNA structure or with proteins/enzymes involved in the regulation of double helix functional processes. In this light, a special focus is given to the quinoline compounds, acting with classical/well-known mechanisms of action (DNA intercalators or Topoisomerase inhibitors). In particular, the quinoline drugs amsacrine and camptothecin (CPT) have been studied as key lead compounds for the development of new agents with improved PK and tolerability properties. Moreover, notable attention has been paid to the quinoline molecules, which are able to interfere with emerging targets involved in cancer progression, as G-quadruplexes or the epigenetic ones (e.g.: histone deacetylase, DNA and histones methyltransferase). The antiproliferative and the enzymatic inhibition data of the reviewed compounds have been analyzed. Furthermore, concerning the SAR (structure-activity relationship) aspects, the most recurrent ligandeprotein interactions are summarized, underling the structural requirements for each kind of mechanism of action. (C) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

Quinoline is a versatile nitrogen heterocycle that can be used to develop antiproliferative agents with different mechanisms of action, such as interfering with DNA structure or proteins/enzymes. Some quinoline compounds have been studied as lead compounds for developing new agents with improved properties. Additionally, there is notable attention to quinoline molecules that interfere with emerging targets involved in cancer progression, providing possibilities for new anticancer agents.