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Biomed Pharmacother ; 63(8): 577-85, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19010640

RESUMO

Dupuytren's disease (DD) is a fibroproliferative disorder, the cure for which is still limited to surgical excision of the affected fascia, often leading to high recurrence rates. Due to this fact, non-surgical treatments are being investigated, among them those targeting molecular processes of proliferation and differentiation in Dupuytren's cell cultures. Drugs with antiproliferative action may be valuable in DD treatment. Through characterization of changes on DD-specific cells, we, therefore, decided to test the therapeutic potential of new cytostatic drugs for DD treatment and/or for reduction of post-operative recurrence rates. The N-sulfonylpyrimidine derivative, amidino-substituted benzimidazo[1,2-a]quinoline, and amidino dihydrothienothienyl[2,3-c]quinolone hydrochloride, known to affect proliferation processes, were tested for their antiproliferative activity on primary fibroblasts/myofibroblasts cell cultures derived from the palmar fascia of patients with DD. Only amidino dihydrothienothienyl[2,3-c]quinolone hydrochloride acted in a highly specific manner on cells derived from diseased fascia of DD patients and exhibited a low cytotoxic effect. This result might be a consequence of its specific activity on cytoskeleton changes occurring in differentiating cells. A similar short-term differential antiproliferative effect was observed by the N-sulfonylpyrimidine derivative that was, however, completely lost after 6- and 14-day treatments. The amidino-substituted benzimidazo[1,2-a]quinoline exerted a strong non-specific, dose-related antiproliferative activity on cell types.


Assuntos
Proliferação de Células/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Contratura de Dupuytren/tratamento farmacológico , Fáscia/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Pró-Fármacos/farmacologia , Estudos de Casos e Controles , Ciclo Celular/efeitos dos fármacos , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Desenho de Fármacos , Contratura de Dupuytren/patologia , Contratura de Dupuytren/cirurgia , Fáscia/patologia , Fasciotomia , Fibroblastos/patologia , Humanos , Concentração Inibidora 50 , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Pró-Fármacos/química , Pró-Fármacos/toxicidade , Pirimidinas/farmacologia , Quinolinas/farmacologia , Quinolonas/farmacologia , Recidiva , Relação Estrutura-Atividade , Fatores de Tempo
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