title: The potential of combi-molecules with DNA-damaging function as anticancer agents.
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.
authors.affiliation: Beijing Key Laboratory of Environmental & Virus Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Environmental & Virus Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Tengjiao
authors.initials: T
authors.lastname: Fan
authors.affiliation: Beijing Key Laboratory of Environmental & Virus Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Lijiao
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Beijing Key Laboratory of Environmental & Virus Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Beijing Key Laboratory of Environmental & Virus Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China.
authors.forename: Rugang
authors.initials: R
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects*; D004337:Drug Carriers; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004791:Enzyme Inhibitors
keywords: DNA-damaging agents; anticancer activity; chemoresistance; combi-molecules; tumor targeting