The potential of combi-molecules with DNA-damaging function as anticancer agents.

The potential of combi-molecules with DNA-damaging function as anticancer agents.

Future Med Chem. 2017 Mar 06;:

Authors: Sun G, Fan T, Zhao L, Zhou Y, Zhong R

Abstract
DNA-damaging agents, such as methylating agents, chloroethylating agents and platinum-based agents, have been extensively used as anticancer drugs. However, the side effects, high toxicity, lack of selectivity and resistance severely limit their clinical applications. In recent years, a strategy combining a DNA-damaging agent with a bioactive molecule (e.g., enzyme inhibitors) or carrier (e.g., steroid hormone and DNA intercalators) to produce a new 'combi-molecule' with improved efficacy or selectivity has been attempted to overcome these drawbacks. The combi-molecule simultaneously acts on two targets and is expected to possess better potency than the parent compounds. Many studies have shown DNA-damaging combi-molecules exhibiting excellent anticancer activity in vitro and in vivo. This review focuses on the development of combi-molecules, which possess increased DNA-damaging potency, anticancer efficacy and tumor selectivity and reduced side reactions than the parent compounds. The future opportunities and challenges in the discovery of combi-molecules were also discussed.

PMID: 28263086 [PubMed - as supplied by publisher]

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