RESUMO
18-amino-4''-O-benzoyl-4'''-N-demethyl-18-deoxospiramycins were designed and synthesized. Synthetic strategy involved selective demethylation of the dimethylamino group in forosamine, benzoylation of the hydroxyl group at the C4'' position and reductive N-amination of the formyl group. Antibacterial characteristics of spiramycin derivatives were tested. The derivatives exhibited promising activity against drug-resistant bacterial strains.
Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Espiramicina/análogos & derivados , Sequência de Carboidratos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Espectrofotometria Infravermelho , Espiramicina/síntese química , Espiramicina/farmacologia , Staphylococcus aureus/efeitos dos fármacosRESUMO
EM703, which is an erythromycin derivative synthesized by our group, has a potent promoting activity of monocyte-to-macrophage differentiation in vitro. Its activity is approximately 300 times higher than that of erythromycin A (EM-A). In this study, we determined three-dimensional (3D) solution structures of EM703 and EM-A, and compared them using a superposition method, in order to investigate the 3D structure-activity relationship. We found a distinct difference between the 3D structures of these molecules, which might be an important factor in their divergent activities.
Assuntos
Eritromicina/análogos & derivados , Imageamento Tridimensional/métodos , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Eritromicina/síntese química , Eritromicina/química , Eritromicina/farmacologia , Humanos , Ligação de Hidrogênio , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Soluções/química , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
This paper concerns a synthetic study of the right-hand segment of complestatin, an inhibitor of gp120-CD4 receptor. The effective synthesis of four important precursors for the right-hand segment of complestatin is described. Two of them are the precursor tripeptides for macrolactamization to the right-hand segment of complestatin at the last step and the other two are the precursor tripeptides for ring-closing reaction using Suzuki and Stille coupling, respectively, to the right-hand segment of complestatin at the last step. These compounds and the synthetic procedure will serve for both the synthesis of the right-hand segment and total synthesis of complestatin in the near future. In addition, consideration of the smooth acidic isomerization of complestatin to chloropeptin was carried out by density functional theory (DFT) calculation.
Assuntos
Clorofenóis/síntese química , Oligopeptídeos/síntese química , Peptídeos Cíclicos/síntese química , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Oligopeptídeos/química , EstereoisomerismoAssuntos
Antibacterianos/farmacologia , Azitromicina/análogos & derivados , Eritromicina/análogos & derivados , Fatores Imunológicos/farmacologia , Macrolídeos/farmacologia , Macrófagos/efeitos dos fármacos , Azitromicina/farmacologia , Linhagem Celular , Eritromicina/farmacologia , Humanos , Relação Estrutura-AtividadeRESUMO
Pinellic acid is a novel and potentially useful oral adjuvant when used in conjunction with intranasal inoculation of influenza HA vaccines. All stereoisomers of pinellic acid have been synthesized via regioselective asymmetric dihydroxylation, regioselective inversion, and stereoselective reduction, and their adjuvant activities were characterized. Among this series of isomers, 9S, 12S, 13S compound has the most potent adjuvant activity. Structure-activity relationships are discussed.
