RESUMO
Naphtho[2,3-f]indole-5,10-dione aminoalkyl derivatives in cytotoxic concentrations inhibit topoisomerase I, which is an important factor of antitumor activity of compounds of this chemical class. The degree of topoisomerase I inhibition with naphtho[2,3-f]indole-5,10-dione derivatives depends on the structure and position of active (aminoalkyl) groups. The mechanism of topoisomerase I inhibition with aminoalkylnaph-tho[2,3-f]indole-5,10-diones differs from specific blocking of the catalytic activity of the enzyme and depends on interactions of these compounds with DNA.
Assuntos
Antraquinonas/farmacologia , Pirróis/farmacologia , Inibidores da Topoisomerase I , Etídio/farmacologia , Relação Estrutura-AtividadeRESUMO
The relationship between the structure of new semisynthetic derivatives of doxorubicin, daunorubicin, and carminomycin and their ability to inhibit topoisomerase 1 were studied. The new derivatives inhibit the activity of topoisomerase 1 at low concentrations, induce the death of K-562 leukemia cells in culture, and produce an antitumor effect in experimental animals with P388 leukemia.