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Rational Design of Alkylating Agents

  • Chapter
Antineoplastic and Immunosuppressive Agents Part I

Abstract

The cytotoxic effects of agents that are able to alkylate biological material under physiological conditions were first reported by Meyer (1887) and Ehrlich (1898), and the application of this class of compounds to the treatment of human cancers was introduced by Gilman and Philips (1946). This followed the observation that derivatives of mustard gas such as HN2 (nitrogen mustard, I) were particularly toxic towards lymphoid tissue and led to the use of such agents in the treatment of lymphatic leukemia. It was later established that other classes of compounds which had comparable alkylating ability, for example, aziridines, epoxides, and alkanesulfonates, also exerted a cytotoxic action on a variety of rapidly dividing cell types (Ross, 1953, 1962). This action is not, however, specific for neoplastic tissue, for all rapidly proliferating cells are affected: normal bone marrow, intestinal mucosa, hair forming cells, and testicular and ovarian tissues are also damaged. The cancer chemotherapist has the problem of modifying the structure of the so-called biological alkylating agents in such a way as to render them specifically cytotoxic towards neoplastic tissue.

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  1. W. C. J. Ross
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  1. Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    Alan C. Sartorelli (Professor) (Professor)

  2. Laboratory of Chemical Pharmacology, National Cancer Institute, National Istitutes of Health, Bethesda, Maryland, 20014, USA

    David G. Johns M. D.

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Ross, W.C.J. (1974). Rational Design of Alkylating Agents. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents Part I. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65678-1_3

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