RESUMO
From the start of the pharmaceutical research natural products played a key role in drug discovery and development. Over time many discoveries of fundamental new biology were triggered by the unique biological activity of natural products. Unprecedented chemical structures, novel chemotypes, often pave the way to investigate new biology and to explore new pathways and targets. This review summarizes the recent results in the area with a focus on research done in the laboratories of Novartis Institutes for BioMedical Research. We aim to put the technological advances in target identification techniques in the context to the current revival of phenotypic screening and the increasingly complex biological questions related to drug discovery.
Assuntos
Produtos Biológicos/farmacologia , Descoberta de Drogas/métodos , Terapia de Alvo Molecular , Animais , Produtos Biológicos/química , Pesquisa Biomédica , Indústria Farmacêutica , Humanos , FenótipoRESUMO
Enterobactin is described in the literature as the typical iron-chelating compound (siderophore) produced by bacteria of the family Enterobacteriaceae. In the course of a HPLC with diode array detection screening programme for detection of novel secondary metabolites, enterobactin, its biosynthetic precursor 2,3-dihydroxy-N-benzoylserine and its linear dimer and trimer condensation products were found to be produced by two Streptomyces strains besides the trihydroxamate-type siderophores desferri-ferrioxamine B and E.
Assuntos
Enterobactina/metabolismo , Streptomyces/metabolismo , Cromatografia Líquida de Alta Pressão , Desferroxamina/química , Enterobacteriaceae/isolamento & purificação , Enterobacteriaceae/metabolismo , Enterobactina/análise , Enterobactina/química , Fermentação , Compostos Férricos/química , Quelantes de Ferro/análise , Sideróforos , Streptomyces/isolamento & purificaçãoRESUMO
Five new piperidine alkaloids (1-5), named streptazones A, B(1), B(2), C, and D, were isolated from Streptomyces strains FORM5 and A1. Their structures were established on the basis of detailed MS and NMR analysis. Streptazone A (1) exhibited significant cytotoxic activity against selected human tumor cell lines.