RESUMO
Non-peptide, small-molecular, non-competitive inhibitors of puromycin-sensitive aminopeptidase (PSA), that is, 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (PAQ-22, 3) and its 1N-methyl analogue (MPAQ-22 4), were structurally modified to afford fluorescent bioprobes, ANTAQ (5) and DAMPAQ-22 (6). The cellular localization of PSA could be visualized by the use of these fluorescent bioprobes.
Assuntos
Aminopeptidases/análise , Corantes Fluorescentes/síntese química , Aminopeptidases/antagonistas & inibidores , Corantes Fluorescentes/química , Humanos , Concentração Inibidora 50 , Cinética , Microscopia de Fluorescência , Puromicina/farmacologia , Quinazolinas/síntese química , Quinazolinas/farmacologia , Células Tumorais CultivadasRESUMO
Pyrimidinyl pyrazole derivatives 1-4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound 2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound 2 and colchicine.
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Ligação Competitiva/efeitos dos fármacos , Colchicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indicadores e Reagentes , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Microtúbulos/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Tubulina (Proteína)/efeitos dos fármacos , Moduladores de Tubulina , Células Tumorais CultivadasRESUMO
3-Substituted (Z)-4-(4-N,N-dialkylaminophenylmethylene)-5(4H)-isoxazolones and related compounds were designed and prepared as candidates for structurally novel androgen antagonists. Several compounds showed potent anti-androgenic activity as assessed by nuclear androgen receptor binding assay and growth inhibition assay using androgen-dependent Shionogi carcinoma cells SC-3. They were approximately 10--220 times more potent than flutamide in these assay systems. They also showed anti-androgenic activity toward prostate tumor cell line LNCaP, which has an aberrant nuclear androgen receptor.