RESUMO
The synthesis and the biological activity of C-1-reduced nigericin derivatives (nigericinols) are described and discussed. The dichloronigericinol 7 impressively demonstrated that the C-1 carboxylic acid moiety was not required for a distinct activity against bacteria and viruses. Based on the correlation between K+/H+ antiport activities and antibacterial activities it was deduced that the mode of action of the described nigericinols are related to their ionophoric properties. Molecular modeling studies showed that the efficiency of the nigericinols as ionophores correlates, qualitatively, with the probability of forming a cyclic structure, with the exception of 7.
Assuntos
Antibacterianos/síntese química , Antivirais/síntese química , Modelos Moleculares , Nigericina/análogos & derivados , Antibacterianos/química , Antibacterianos/farmacologia , Antivirais/química , Antivirais/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Estrutura Molecular , Nigericina/síntese química , Nigericina/química , Nigericina/farmacologia , Simplexvirus/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The anticoccidial activity of semduramicin against laboratory isolates of five species of poultry Eimeria was investigated. In laboratory scale battery trials, semduramicin at 20 to 30 ppm demonstrated broad-spectrum anticoccidial efficacy equivalent to salinomycin at 60 ppm. Also, semduramicin at 25 ppm was fed to uninfected cockerels in batteries for 21 days, and growth rate and feed efficiency were found to be equivalent to birds fed salinomycin at 60 ppm. Semduramicin was well tolerated when coadministered with tiamulin. Semduramicin demonstrated the same activity whether produced by semisynthesis or by direct fermentation.
Assuntos
Galinhas/parasitologia , Coccidiose/veterinária , Eimeria tenella/efeitos dos fármacos , Nigericina/análogos & derivados , Doenças das Aves Domésticas/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Coccidiose/tratamento farmacológico , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Quimioterapia Combinada/farmacologia , Quimioterapia Combinada/uso terapêutico , Ionóforos/farmacologia , Ionóforos/uso terapêutico , Masculino , Nigericina/síntese química , Nigericina/farmacologia , Nigericina/uso terapêuticoRESUMO
A number of derivatives of mutalomycin (1), a naturally occurring polyether antibiotic, have been synthesized. In the desulfurization reaction of the ethylthio derivative (5) of mutalomycin (1) with Raney-nickel we observed an unusual course of the reaction, namely the introduction of a hydroxy group instead of the usual exchange against hydrogen, leading to two reaction products, mutalomycin (1) and 28-epimutalomycin (3). The structure of 3 and 2-epimutalomycin (2), both minor metabolites from the mutalomycin fermentation, were elucidated by X-ray analysis.
