RESUMO
A new series of 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes were designed and synthesized. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Sixteen of these new compounds exhibited comparable or better anti-inflammatory activities than aspirin suggesting that they can be further developed as potential anti-inflammatory drug leads. In addition, treatment with these anti-inflammatory agents did not prolong tail bleeding time in mice. The structure/activity relationships were also analyzed among these compounds. Considering their good efficacy and safety profiles, some 5-glycylamino-2-substituted-phenyl-1,3-dioxacycloalkanes are worthy to be explored further in assessing the possible link between anti-inflammation and cancer prevention.
Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Inflamação/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/síntese química , Derivados de Benzeno , Quimioprevenção/métodos , Camundongos , Relação Estrutura-Atividade , Resultado do TratamentoRESUMO
A new series of optically pure 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes were designed and synthesized via a chemo-enzymatic combined method to develop new chemoprevention agents. Twenty-four of newly synthesized compounds significantly inhibited xylene-induced rat ear edema and exhibited comparable or better anti-inflammatory activities than the reference drug aspirin. Treatment of these anti-inflammatory agents did not prolong the tail bleeding time in rat. In addition, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes exhibited good membrane permeability based on in vitro Caco-2 cell monolayer permeability assay. Furthermore, some preliminary structure-activity relationships were further analyzed among these compounds. Taken together, 5-amino-2-substitutedphenyl-1,3-dioxacycloalkanes may represent a new class of anti-inflammatory drugs with safer pharmacological profile.
Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Hidrocarbonetos Cíclicos/síntese química , Hidrocarbonetos Cíclicos/farmacologia , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Aspirina/uso terapêutico , Tempo de Sangramento , Permeabilidade da Membrana Celular/efeitos dos fármacos , Quimioprevenção , Cromatografia Líquida de Alta Pressão , Desenho de Fármacos , Edema/induzido quimicamente , Edema/patologia , Hidrocarbonetos Cíclicos/química , Masculino , Camundongos , Estrutura Molecular , Oxigênio/química , Proteína Quinase C/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Xilenos/toxicidadeRESUMO
A new class of 2,5-disubstituted-dioxacycloalkanes were designed and synthesized via stereoselective synthetic method as cancer chemoprevention agents. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model. Some of these compounds exhibited comparable or better anti-inflammatory activities than that of aspirin suggesting that they can be further developed as potential anti-inflammatory drug lead compounds. In addition, treatment of these anti-inflammatory agents did not prolong tail bleeding time in mice. The structure/activity relationships were also analyzed among these compounds.
Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Cicloparafinas/síntese química , Cicloparafinas/farmacologia , Desenho de Fármacos , Oxigênio/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Tempo de Sangramento , Quimioprevenção , Cicloparafinas/química , Cicloparafinas/uso terapêutico , Edema/tratamento farmacológico , Edema/patologia , Masculino , Camundongos , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
A class of 5-trifluoroacetylamino-1,3-dioxacycloalkanes, 5-benzoylamino-1,3-dioxacycloalkanes, and 5-amino-1,3-dioxacycloalkane compounds were stereoselectively synthesized as potential anti-inflammatory drug candidates. The anti-inflammatory activities of these compounds were tested using the xylene-induced mouse ear edema model, from which multiple compounds possessing anti-inflammatory properties which surpass aspirin were identified; these compounds were then compared to establish structure-activity relationships.
