RESUMO
A new series of [4-(2-phenylethenesulfonylmethyl)phenyl]quinazolin-4-yl-amines was prepared and tested for its in vitro cytotoxic activity against a panel of 12 human cancer cell lines. Compounds 9, 15, 24 and 31 showed good in vitro activity and were further tested for their in vivo efficacy in the HT-29 human colon adeno carcinoma xenograft model. Compound 9 exhibited promising activity in this model. Dose-response studies for this compound against HT-29 human colon adeno carcinoma xenografts at 100, 200 and 400mg/kg doses were performed.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/síntese química , Quinazolinas/administração & dosagem , Quinazolinas/síntese química , Administração Oral , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Células HT29 , Humanos , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Ensaios Antitumorais Modelo de Xenoenxerto/estatística & dados numéricosRESUMO
A series of 6,7-diphenyl-2,3,8,8a-tetrahydro-1H-indolizin-5-one analogues were synthesized and evaluated for cytotoxic activity against eight human cancer cell lines. Compounds 18, 21, 28, 29, 30 and 31 showed cytotoxic activity with GI(50) values in the range of 2.1-8.1 microM concentration. Among these, compounds 21 and 28 exhibited good pharmacokinetic properties. These compounds were further evaluated for their in vivo efficacy in modified hollow fibre assay (HFA).
Assuntos
Antineoplásicos/síntese química , Indolizinas/síntese química , Indolizinas/farmacologia , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Humanos , Indolizinas/farmacocinética , Camundongos , Farmacocinética , Relação Estrutura-AtividadeRESUMO
In our endeavor to design and synthesize novel anticancer agents, a new series of indoloquinazoline compounds were prepared and tested initially for anticancer activity in vitro against a panel of human cancer cell lines. Most of these compounds exhibited cytotoxic activity in in vitro screens. Compounds were selected and further evaluated using a modified Hollow Fiber Assay for their preliminary in vivo activity against 12 cell lines implanted in the subcutaneous and intraperitoneal compartments in mice. The results indicate that these compounds may constitute a new class of anticancer agents.
