RESUMO
A novel synthetic strategy is described which may be used to prepare analogues of the antimalarial, fungal metabolite apicidin. Compared to the natural product, one analogue shows potent and selective activity in vitro against the parasite Trypanosoma brucei and low mammalian cell toxicity.
Assuntos
Peptídeos Cíclicos/síntese química , Tripanossomicidas/síntese química , Animais , Testes de Sensibilidade Parasitária , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacosRESUMO
Proton decoupled, cross-polarization magic-angle spinning 13C NMR spectra of four polymorphic forms (A, B, C, and D) and a monohydrate form (M1) of the histamine H2 antagonist cimetidine were obtained, and the chemical shifts of the various forms were tabulated. A modified polarization inversion pulse sequence was used to distinguish quaternary, methine, methylene, and methyl carbon resonances and thereby assist spectral assignment. It is also shown that the solid-state form of cimetidine in a commercial formulation can be reliably ascertained by NMR, despite the presence in the spectrum of signals from organic excipients that are much more intense than those from the compound.