RESUMO
A cancer-targeting conjugate 4 of a cyclometalated [N,C,N-Pt(II)] complex bearing a NËCËN 1,3-di(2-pyridyl)-benzene with c(RGDyK) peptide as guiding molecule was designed and synthesized for real-time drug delivery monitoring in cancer cells and photodynamic therapy (PDT). This conjugate demonstrates a mild cytostatic effect to six cancer cell lines expressing integrins at different extent, while possessing promising features for PDT. Conjugate 4 demonstrated rapid cell uptake by receptor-mediated endocytosis and efficient generation of 1O2 upon irradiation. Incubation of rat bladder cancer cells AY27 with conjugate 4 (50 µΜ) prior to blue light exposure (5 min) resulted in significant reduction (50%) of cell survival compared to control cells as measured by MTT assay post 24 h after treatment.
Assuntos
Antineoplásicos/farmacologia , Integrinas/antagonistas & inibidores , Oligopeptídeos/farmacologia , Compostos Organoplatínicos/farmacologia , Fotoquimioterapia , Platina/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Integrinas/metabolismo , Estrutura Molecular , Oligopeptídeos/química , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Platina/química , Ratos , Relação Estrutura-AtividadeRESUMO
An efficient method for the synthesis of spiro-N,O-ketals with 5- and 6-membered rings was developed via a gold-catalyzed spiroamidoketalization of alkynyl amidoalcohols under mild conditions. This methodology has been successfully applied to the synthesis of a spiro-N,O-ketal analogue of marineosin A.
