Antibiotic Drugs Aminoglycosides Cleave DNA at Abasic Sites: Shedding New Light on Their Toxicity?.

Abasic sites are probably the most common lesions in DNA resulting from the hydrolytic cleavage of glycosidic bonds that can occur spontaneously and through DNA alkylation by anticancer agents, by radiotherapy, and during the repair processes of damaged nucleic bases. If not repaired, the abasic site can be mutagenic or lethal. Thus, compds. able to specifically bind and react at abasic sites have attracted much attention for therapeutic and diagnostic purposes. Here, we report on the efficient cleavage activity of characteristic antibiotic drugs of the major aminoglycosides (AG) family at abasic sites introduced either by depurination in a plasmid DNA or site specifically in a synthetic oligonucleotide. Among the antibiotic AG drugs selected for this study, neomycin B is the most efficient (a 0.1 $μ$M concn. induces 50{%} cleavage of an abasic site contg. DNA). This cleavage activity could be related to aminoglycoside toxicity but also find medicinal applications through potentiation of cancer radiotherapy and chemotherapy with alkylating drugs. In the search for antibiotic and antiviral agents, we have previously described the synthesis of derivs. of the small aminoglycoside neamine, which corresponds to rings I and II of neomycin B constituted of four rings. The cleavage activity at abasic sites of four of these neamine derivs. is also reported in the present study. One of them appeared to be much more active than the parent compd. neamine with cleavage efficiency close to that of neomycin. [on SciFinder(R)]

Références

Titre
Antibiotic Drugs Aminoglycosides Cleave DNA at Abasic Sites: Shedding New Light on Their Toxicity?.
Type de publication
Article de revue
Année de publication
2013
Revue
Chem. Res. Toxicol.
Volume
26
Pagination
1710–1719
ISSN
0893-228X
Soumis le 12 avril 2018