Mitomycin C (Fig. 10.24) was isolated from Streptomyces caespitosus in 1958 by Japanese workers and is considered the prototype of the bioreductive alkylating agents.137139 Mitomycin is sometimes included as an alkylating agent but is included here because it is a naturally occurring material. The drug contains what would appear to be reactive functionalities, including the quinone and aziridine functionalities, both or which would be thought to be susceptible to nucleophilic attack; however, the reactivity of these functionalities is reduced because of steric and electronic effects in the parent molecule. It was reasoned that selective activation could be achieved in a reductive environment such as that found in an area of low oxygen content. This is known to occur in tumors where the fast-growing cells often grow beyond the blood supply that would normally provide oxy-gen.140 A normal cell would undergo apoptosis under these conditions, but because cancer cells often have their apo-ptotic mechanisms inhibited they continue to survive with little or no oxygen available. Mitomycin C is capable of being activated and alkylating DNA in an anaerobic environ
Figure 10.24 • Structure of mitomycin C.
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