Zhi-Qiang Xia

Indole- and indolizine-glyoxylamides displaying cytotoxicity against multidrug resistant cancer cell lines

We report herein the SAR studies of a series of indole- and indolizine-glyoxylamides that demonstrate substantial in vitro anti-proliferative activities against cancer cell lines, including multidrug resistance (MDR) phenotypes. The in vitro cytotoxic effects have been demonstrated across a wide array of tumor types of various origins (e.g., breast, colon, uterine).

Novel indolizine compounds as potent inhibitors of phosphodiesterase IV (PDE4): structure–activity relationship

A series of novel indolizine 2-oxoacetamides were designed and synthesized as PDE4 inhibitors. Preliminary SAR of this new class of compounds revealed key structural features required for high potency. Compounds 1ab and 2a are among the most potent inhibitors of PDE4 with low single nM IC50. Cellular activity was demonstrated by the inhibition of TNFα production from human PBMC with IC50 ranging from 14 to 72 nM. Docking analyses suggest the OH group in 1ab enhance the binding via an H-bond interaction with the PDE4 enzyme.

Synthesis, crystallographic characterization and electrochemical property of a copper(II) complex of the anticancer agent elesclomol.

Elesclomol is a novel anticancer agent that has been evaluated in a number of late stage clinical trials. A new and convenient synthesis of elesclomol and its copper complex is described. X-ray crystallographic characterization and the electrochemical properties of the elesclomol copper(II) complex are discussed. The copper(II) cation is coordinated in a highly distorted square-planar geometry to each of the sulphur and amide nitrogen atoms of elesclomol. Electrochemical measurements demonstrate that the complex undergoes a reversible one-electron reduction at biologically accessible potentials. In contrast the free elesclomol is found electrochemically inactive. This evidence is in strong support of the mechanism of action we proposed for the anticancer activity of elesclomol.