RESUMO
In the previous article we have reported that 3,4-dihydroquinazoline 1 is a potent and selective T-type calcium channel blocker that exhibited strong anti-cancer activity in vitro. Compound 1·2HCl was further in vivo evaluated against A549 xenograft in BALB/c nude mice, which exhibited 49% tumor-weight inhibition through intravenous administration of 2 mg/kg of body weight and was more potent than doxorubicin. Moreover, compound 1·2HCl has an oral bioavailability of 98% with LD(50) values of 693 mg/kg (p.o. route) and 40.0 mg/kg (i.v. route) of body weight. In addition, its efficient scale-up synthetic method was developed.
Assuntos
Antineoplásicos/farmacologia , Quinazolinas/farmacologia , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Dose Letal Mediana , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante HeterólogoRESUMO
First total synthesis of methylgerambullone (MGB, 1) isolated from Glycosmis angustifolia was completed via a convergent route. The effect of MGB on the contractile responses of the isolated guinea-pig ileum induced by acetylcholine was investigated. As a result, it showed a potent relaxation rate (78.66+/-4.30% at 100mg/L) in a concentration-dependent manner on longitudinal smooth muscle contraction of isolated guinea-pig ileum induced by 1microM acetylcholine.
Assuntos
Acrilamidas/síntese química , Produtos Biológicos/síntese química , Sulfonas/síntese química , Acetilcolina/farmacologia , Acrilamidas/química , Acrilamidas/farmacologia , Animais , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cobaias , Ílio/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Rutaceae/química , Sulfonas/química , Sulfonas/farmacologiaRESUMO
In order to further clarify the role of T-type Ca(2+) channels in cell proliferation, we have measured the growth inhibition of human cancer cells by using our potent T-type Ca(2+) channel blockers. As a result, KYS05090, a most potent T-type Ca(2+) channel blocker, was found to be as potent as doxorubicin against some human cancer cells without acute toxicity. Therefore, this letter provides the biological results that T-type calcium channel is important in regulating the important cellular phenotype transition leading to cell proliferation, and thus novel T-type Ca(2+) channel blocker presents new prospects for cancer treatment.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Bloqueadores dos Canais de Cálcio/síntese química , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo T/química , Ensaios de Seleção de Medicamentos Antitumorais , Quinazolinas/farmacologia , Animais , Canais de Cálcio Tipo T/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Química Farmacêutica/métodos , Doxorrubicina/farmacologia , Desenho de Fármacos , Humanos , Concentração Inibidora 50 , Camundongos , Modelos Químicos , Quinazolinas/síntese químicaRESUMO
In the chiral Co(III)(salen)-catalysed HKR of racemic epoxides, in the presence of ionic liquids, Co(II)(salen) complex is oxidised without acetic acid to catalytically active Co(III)(salen) complex during reaction and, moreover, this oxidation state is stabilised against reduction to Co(II) complex which enables the reuse of the recovered catalyst for consecutive reactions without extra reoxidation.