Clinical applications of quinone-containing alkylating agents.
Quinone-containing alkylating agents are a class of chemical agents that have received considerable interest as anticancer drugs. These agents contain a quinone moiety that can be reduced and an alkylating group that can form covalent bonds with a variety of cellular components. The oxidation state of the quinone element can modulate the activity of the alkylating element, and reduction of the quinone is required for activation of the alkylating activity of many of these agents. The quinone element may also contribute to the cytotoxic activity of quinone-containing alkylating agents through the formation of reactive oxygen species during redox cycling. The natural product, mitomycin C, has been the most widely used quinone-containing alkylating agent in the clinic, but other quinone-containing alkylating agents like porfiromycin, diaziquone, carbazilquinone, triaziquone and EO9 have also been used in the clinic for the treatment of cancer. In addition, many other quinone-containing alkylating agents have been tested in preclinical studies and the development of new agents is being actively pursued. This chapter describes the current and past clinical uses of these agents in the treatment of cancer and discusses new agents that are currently in clinical trials.
Begleiter
A
A
Manitoba Institute of Cell Biology, CancerCare Manitoba and the Departments of Internal Medicine and Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000266:history; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000266:history; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000266:history; D001388:Aziridines / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000266:history; D016227:Benzoquinones / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000266:history; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D049673:History, 20th Century; D006801:Humans; D045563:Indolequinones; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000266:history; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000266:history; D009369:Neoplasms / Q000188:drug therapy* / Q000266:history; D011809:Quinones / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D001388:Aziridines; D016227:Benzoquinones; D045563:Indolequinones; D007211:Indoles; D011809:Quinones; D016685:Mitomycin; C060817:apaziquone