RESUMO
Novel simplified analogues of the potent RNA polymerase inhibitor etnangien were obtained by total synthesis and evaluated for antibacterial activity against Gram-positive bacteria and one Gram-negative bacterium.
Assuntos
RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Desenho de Fármacos , Macrolídeos/síntese química , Macrolídeos/farmacologia , Polienos/síntese química , Polienos/farmacologia , RNA Polimerases Dirigidas por DNA/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/enzimologia , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
An efficient and modular one-pot synthesis of polysubstituted aromatic amines by a mild reductive amination procedure is described and the biological potential of these nitrogen-centered compounds is demonstrated by growth inhibition of murine connective tissue cells and microscopy-based morphological studies.
Assuntos
Aminas/síntese química , Aminas/toxicidade , Citotoxinas/síntese química , Citotoxinas/toxicidade , Aminas/química , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citotoxinas/química , Avaliação Pré-Clínica de Medicamentos , Camundongos , Estrutura Molecular , Potoroidae , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
The novel phenylanthraquinones 4'-O-demethylknipholone-4'-O-beta-D-glucopyranoside (2) and gaboroquinones A (3) and B (4) were isolated from the African medicinal plant Bulbine frutescens. Biaryl 2 represents the first phenylanthraquinone glucoside, while 3 and 4 are the first side-chain-hydroxylated phenylanthraquinones. Their constitutions were determined by spectroscopic analysis, in particular by HMBC, HMQC, and ROESY NMR investigations, and by chemical transformations. The axial configurations were elucidated chemically, by deglucosylation of 2 and by side-chain deoxygenation of 3 and 4 to give the known phenylanthraquinones 4'-O-demethylknipholone (5), isoknipholone (6), and knipholone (1), respectively, and chiroptically, by CD investigations. Compounds 2, 3, and 4 showed moderate to good antiplasmodial and antitrypanosomal activities in vitro.