Targeting Heme for the Identification of Cytotoxic Agents

Title:Targeting Heme for the Identification of Cytotoxic Agents

Volume: 13 Issue: 3

Author(s): Shiming Zhang, Hui Chen, Jessica Webster and Glenn S. Gerhard

Affiliation:

Keywords: Heme, Target, Cancer, High-throughput screen, Cytotoxicity

Abstract: Certain tumor types have an increased capacity for heme synthesis, which serves as the basis for photodynamic therapy. Heme also serves as the target for the anti-malaria drug artemisinin, which has also been used as an anti-cancer drug. We developed a highthroughput screening assay to identify heme interacting (HI) compounds, which included imidazole, pyridine, carbonitrile, isocyanide, and quinoline core structures that are known to interact with heme or hemin. The cytotoxicity of several of the compounds towards human leukemia cell lines could be modulated by increasing or decreasing heme synthesis. Spectral analysis indicated that distinct molecular interactions occurred with heme, suggesting that HI compounds appear to target heme with exquisite specificity. These studies suggest that heme may serve as a novel therapeutic target for cancer drug discovery.

Cite this article as:

Zhang Shiming, Chen Hui, Webster Jessica and S. Gerhard Glenn, Targeting Heme for the Identification of Cytotoxic Agents, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (3) . https://dx.doi.org/10.2174/1871520611313030014