Antiangiogenic properties of substituted (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol/one analogs and their derivatives.

A series of substituted (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ols (1a–1k), (Z)-2-benzylindol-3yl-methylene)quinuclidin-3-ones (2a–2i), (Z)-(±)-2-(1H/N-methyl-indol-3-ylmethylene)quinuclidin-3-ol (3b), and substituted (Z)-(±)-2-(N-benzenesulfonylindol-3-yl-methylene)quinuclidin-3-ols and their derivatives (4a–4d) that incorporate a variety of substituents in both the indole and N-benzyl/benzene sulfonyl moieties were evaluated for their antiangiogenic activity using Human Umbilical Vein Endothelial Cells (HUVECs). Eight analogs were identified as potent angiogenesis inhibitors at a non-toxic concentration of 10μM. The analog, 4b was identified as the most potent antiangiogenic agent. The mechanism of inhibition is consistent with inhibition of ENOX activity.