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DNA Minor Groove Alkylating Agents

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Abstract:

Recent work on a number of different classes of anticancer agents that alkylate DNA in the minor groove is reviewed. There has been much work with nitrogen mustards, where attachment of the mustard unit to carrier molecules can change the normal patterns of both regio- and sequence-selectivity, from reaction primarily at most guanine N7 sites in the major groove to a few adenine N3 sites at the 3-end of poly(A(slash)T) sequences in the minor groove. Carrier molecules discussed for mustards are intercalators, polypyrroles, polyimidazoles, bis(benzimidazoles), polybenzamides and anilinoquinolinium salts. In contrast, similar targeting of pyrrolizidine alkylators by a variety of carriers has little effect of their patterns of alkylation (at the 2-amino group of guanine). Recent work on the pyrrolobenzodiazepine and cyclopropaindolone classes of natural product minor groove binders is also reviewed.

Keywords: Anilinoquinolinium; CBI compounds; DNA Minor Groove Alkylating Agents; Intercalators; Polybenzamides; Polypyrroles; Pyrrolizidines

Document Type: Review Article

DOI: https://doi.org/10.2174/0929867003373283

Publication date: 2000-05-01

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