RESUMO
Novel series of limonin derivatives (V-A-1-V-A-8, V-B-1-V-B-8) were synthesized by adding various tertiary amines onto the C (7)-position of limonin. The synthesized compounds possessed favorable physicochemical property, and the intrinsic solubility of the novel compounds were significantly improved, compared with limonin. Different pharmacological models were used to evaluate the analgesic and anti-inflammatory activities of the target compounds. Compound V-A-8 exhibited the strongest in vivo activity among the novel limonin analogs; its analgesic activity was more potent than aspirin and its anti-inflammatory activity was stronger than naproxen under our testing conditions.
Assuntos
Analgésicos/química , Anti-Inflamatórios/química , Limoninas/química , Analgésicos/administração & dosagem , Analgésicos/síntese química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/síntese química , Descoberta de Drogas , Edema/tratamento farmacológico , Humanos , Limoninas/administração & dosagem , Limoninas/síntese química , Camundongos , Estrutura Molecular , Dor/tratamento farmacológicoRESUMO
A novel series of benzimidazol-2-yl or benzimidazol-2-ylthiomethyl benzoylguanidines were designed and synthesized as Na(+)/H(+)exchanger inhibitors. Most of them were found to inhibit NHE1-mediated platelet swelling in a concentration-dependent manner, and to have significant cardioprotective effect against myocardial ischemic-reperfusion injury, among which compounds 10a and 34 were more potent than cariporide in both in vivo and in vitro tests.