RESUMO
DNA interstrand cross-linking (ICL) agents are an important group of cytotoxic drugs with the capability of binding covalently between two strands of DNA, thereby preventing vital processes such as replication or transcription in dividing cells. In anticancer therapy however, their potential is limited due to the resistance by various mechanisms. In order to develop highly effective antitumor drugs it is necessary to study both effective ICL formations and their subsequent repair mechanisms. This review presents an overview of development over the past decade and the use of both well-known and new DNA interstrand cross-linking agents. Their potential in applications especially as anticancer chemotherapeutics in the framework of current knowledge of repair mechanisms and development of combined chemotherapy is discussed.
Assuntos
Antineoplásicos/química , Reagentes de Ligações Cruzadas/química , DNA/metabolismo , Alcaloides/química , Alcaloides/uso terapêutico , Antraquinonas/química , Antraquinonas/uso terapêutico , Antineoplásicos/uso terapêutico , Azepinas/química , Azepinas/uso terapêutico , Aziridinas/química , Aziridinas/uso terapêutico , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Reagentes de Ligações Cruzadas/uso terapêutico , DNA/química , Reparo do DNA , Humanos , Mecloretamina/química , Mecloretamina/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
2-Phenyl-3-hydroxy-4(1H)-quinolinones can be considered as aza-analogues of flavones, compounds which are known for the wide-range of their biological activity. These quinolinones were studied as inhibitors of topoisomerase, gyrase and IMPDH. They were tested for anticancer activity in-vitro and were also shown to possess immunosuppressive properties. This review is the first summarizing the synthesis and activity of the mentioned quinolinones.