Synthesis of directly linked diazine isosteres of pyrrole-polyamide that photochemically cleave DNA

Ong, Chi Wi, Yang, Ya-Ting, Liu, Meng-Chi, Fox, Keith R., Liu, Ping Hao and Tung, Hung-Wei (2012) Synthesis of directly linked diazine isosteres of pyrrole-polyamide that photochemically cleave DNA. Organic & Biomolecular Chemistry, 10 (5), 1040. (doi:10.1039/c1ob06803b).

Abstract

A distamycin model containing an isosteric diazine linked pyrrole has been designed and synthesized. The key steps of the synthesis involved the successful diazotization of the 4-amino-pyrrole derivatives to give the diazomium salts, which undergo coupling reactions with N-methylpyrrole to yield the directly linked diazine compounds. The amide isosteric-diazine pyrrole I demonstrated photo-induced DNA damage upon iradiation with UV light (365 nm). Spectrophotometric and mass spectrometric identification suggest that the azo-linkage in I did not dissociate during irradiation. Moreover, compound I produced DNase I footprints with the HexB DNA fragment at AT sites, as well as some other mixed sequences (5?-ATGTCG-3?), indicative of the additional role of the diazine-linkage for interaction at the duplex DNA

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Contributors

Author: Keith R. Fox

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