A review. Analogs of naturally occurring antitumor agents, such as distamycin A, which bind in the minor groove of DNA, represent a new class of anticancer compds. currently under investigation. Distamycin A has driven researcher's attention not only for their biol. activity, but also for its non intercalative binding to the minor groove of double-stranded B-DNA, where it forms strong reversible complex preferentially at the nucleotide sequences consisting of 4-5 adjacent AT base pairs. The pyrrole-amide skeleton of distamycin A was also used as DNA sequence selective vehicles for the delivery of alkylating functions to DNA targets, leading to a sharp increase of its cytotoxicity, in comparison to that, very weak, of distamycin itself. In the last few years, several hybrid compds., in which known antitumor derivs. or simple active moieties of known antitumor agents were tethered to distamycin frames, were designed, synthesized, and tested. Several efforts were made to modify DNA sequence selectivity and stability of the distamycin and the structural modifications were based on replacement of pyrrole by other heterocycles and/or benzoheterocycles obtaining a novel class of minor groove binding mols. called lexitropsins. The role of the amidino moiety, by the substitution with various groups, which includes ionizable, acid or basic, and non-ionizable groups, was also studied. The synthesis of a hybrid deriving among the combination of the distamycin A and naturally occurring alkylating agent was also reported. Several classes of distamycin derivs. that were reported in the published literature were described in this review article.

Distamycin A as stem of DNA minor groove alkylating agents

BARALDI, Pier Giovanni;ROMAGNOLI, Romeo
2004

Abstract

A review. Analogs of naturally occurring antitumor agents, such as distamycin A, which bind in the minor groove of DNA, represent a new class of anticancer compds. currently under investigation. Distamycin A has driven researcher's attention not only for their biol. activity, but also for its non intercalative binding to the minor groove of double-stranded B-DNA, where it forms strong reversible complex preferentially at the nucleotide sequences consisting of 4-5 adjacent AT base pairs. The pyrrole-amide skeleton of distamycin A was also used as DNA sequence selective vehicles for the delivery of alkylating functions to DNA targets, leading to a sharp increase of its cytotoxicity, in comparison to that, very weak, of distamycin itself. In the last few years, several hybrid compds., in which known antitumor derivs. or simple active moieties of known antitumor agents were tethered to distamycin frames, were designed, synthesized, and tested. Several efforts were made to modify DNA sequence selectivity and stability of the distamycin and the structural modifications were based on replacement of pyrrole by other heterocycles and/or benzoheterocycles obtaining a novel class of minor groove binding mols. called lexitropsins. The role of the amidino moiety, by the substitution with various groups, which includes ionizable, acid or basic, and non-ionizable groups, was also studied. The synthesis of a hybrid deriving among the combination of the distamycin A and naturally occurring alkylating agent was also reported. Several classes of distamycin derivs. that were reported in the published literature were described in this review article.
2004
Baraldi, Pier Giovanni; Nunez, Md; Espinosa, A; Romagnoli, Romeo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/516478
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