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The leaving group strongly affects H?O?-induced DNA cross-linking by arylboronates.

ABSTRACT: We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H2O2-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs.

SUBMITTER: Cao S

PROVIDER: S-EPMC3939700 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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The leaving group strongly affects H₂O₂-induced DNA cross-linking by arylboronates.

Cao Sheng S Wang Yibin Y Peng Xiaohua X

The Journal of organic chemistry 20140106 2

We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H2O2-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and step ...[more]

PMID: 24378073

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