期刊
NITRIC OXIDE-BIOLOGY AND CHEMISTRY
卷 43, 期 -, 页码 8-16出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.niox.2014.07.005
关键词
Diazeniumdiolate; Prodrug; Drug delivery; Enzyme; Glutathione
Nitric oxide (NO) is a reactive gaseous free radical which mediates numerous biological processes. At elevated levels, NO is found to be toxic to cancers and hence, a number of strategies for site-directed delivery of NO to cancers are in development during the past two decades. More recently, the focus of research has been to, in conjunction with other cancer drugs deliver NO to cancers for its secondary effects including inhibition of cellular drug efflux pumps. Among the various approaches toward site-selective delivery of exogenous NO sources, enzyme activated nitric oxide donors belonging to the diazeniumdiolate category afford unique advantages including exquisite control of rates of NO generation and selectivity of NO production. For this prodrug approach, enzymes including esterase, glutathione/glutathione S-transferase, DT-diaphorase, and nitroreductase are utilized. Here, we review the design and development of various approaches to enzymatic site-directed delivery of NO to cancers and their potential. (c) 2014 Elsevier Inc. All rights reserved.
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