Development of Radiosensitizers: A Medicinal Chemistry Perspective

• Published in: Advances in Pharmacology Vol. 19; pp. 155 - 206
• Main Authors: Narayanan, V.L., Lee, William W.
• Format: Book Chapter Journal Article
• Language: English
• Published: United States Elsevier Inc 1982; Elsevier Science & Technology
• Subjects: Animals; Electrons; Heterocyclic Compounds - chemical synthesis; Humans; Hypoxia - prevention & control; Nitrobenzenes - pharmacology; Nitroimidazoles - pharmacology; Pharmacology; Radiation-Sensitizing Agents - chemical synthesis; Radiation-Sensitizing Agents - metabolism; Radiation-Sensitizing Agents - toxicity; Solubility; Structure-Activity Relationship
• ISBN: 9780120329199; 0120329190
• ISSN: 1054-3589; 0065-3144; 1557-8925
• DOI: 10.1016/S1054-3589(08)60023-X

This chapter discusses the development of radiosensitizers. Radiosensitizers are chemicals that sensitize hypoxic tumor cells to radiation. Electron affinic radiosensitizers are the most promising of the several classes of radiosensitizers summarized in the Division of Cancer Treatment (DCT), National Cancer Institute (NCI), Linear Array, Radiosensitizers, February 1978. The objective of this chapter is to critically review electron affinic radiosensitizers from the medicinal chemist's perspective with the goal of discovering new clinically useful radiosensitizers. As such the chapter integrates the concepts and research results available on this subject from the physicochemical, radiobiological, structure-activity, synthesis, pharmacological, and clinical points of view. The presence of radioresistant hypoxic cells in the tumor is believed to be a major cause of the failure of radiation therapy. Hypoxic cells lack oxygen either chronically or acutely and this fact affords them protection against radiation. Cells are chronically hypoxic because the oxygen, supplied by capillaries, has been depleted by the metabolism of intervening cells.