Substituted oxines inhibit endothelial cell proliferation and angiogenesis.

Two substituted oxines, nitroxoline (5) and 5-chloroquinolin-8-yl phenylcarbamate (22), were identified as hits in a high-throughput screen aimed at finding new anti-angiogenic agents. In a previous study, we have elucidated the molecular mechanism of antiproliferative activity of nitroxoline in endothelial cells, which comprises of a dual inhibition of type 2 human methionine aminopeptidase (MetAP2) and sirtuin 1 (SIRT1). Structure-activity relationship study (SAR) of nitroxoline offered many surprises where minor modifications yielded oxine derivatives with increased potency against human umbilical vein endothelial cells (HUVEC), but with entirely different as yet unknown mechanisms.

Inhibition of heme crystal growth by antimalarials and other compounds: implications for drug discovery.

During intraerythrocytic infection, Plasmodium falciparum parasites crystallize toxic heme released during hemoglobin catabolism. The proposed mechanism of quinoline inhibition of crystal growth is either by a surface binding or a substrate sequestration mechanism. The kinetics of heme crystal growth was examined in this work using a new high-throughput crystal growth determination assay based on the differential solubility of free vs.