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• W2897077180 abstract "We identified low-molecular weight compounds derived from the antimicrobial peptide human neutrophil peptide-1 that bind to Lipid II, an essential precursor of bacterial cell wall biosynthesis. These compounds act as antibacterials on multiple biosynthesis pathways with specificity against gram-positive organisms. Here, we have tested a small subset of our most promising leads against the bacterium Clostridium perfringens and sporozoites of Eimeria tenella, an intracellular protozoan parasite that causes intestinal disease in poultry. We found one compound, 1611-0203 (2-{2,3,5,6-tetrafluoro-4-[2,3,5,6-tetrafluoro-4-(2-hydroxyphenoxy)phenyl]phenoxy}phenol), specifically to inhibit growth of both agents out of all compounds tested. Additionally, compound 1611-0203 inhibits Staphylococcus aureus and Enterococcus spp. Mechanism-of-action studies further reveal that 1611-0203 affects cell wall biosynthesis and inhibits additional biosynthetic pathways. Combined, our results indicate that compounds such as 1611-0203 have therapeutic potential to act as anti-infectives against various organisms simultaneously.Efectos anti infecciosos pleiotrópicos de los compuestos antimicrobianos derivados de la defensina. Se identificaron compuestos de bajo peso molecular derivados del péptido antimicrobiano, péptido neutrófilico humano 1 que se unen al lípido II, que es un precursor esencial de la biosíntesis de la pared celular bacteriana. Estos compuestos actúan como antibacterianos en múltiples vías de biosíntesis con especificidad contra organismos Gram positivos. En este estudio se probó un pequeño subconjunto de los proyectos más prometedores contra la bacteria Clostridium perfringens y los esporozoitos de Eimeria tenella, que es un parásito protozoario intracelular que causa enfermedad intestinal en aves comerciales. Se encontró un compuesto, 1611-0203 (2-{2,3,5,6-tetrafluoro-4-[2,3,5,6-tetrafluoro-4-(2-hidroxifenoxi)fenil]fenoxi}fenol), específicamente para inhibir el crecimiento de ambos agentes de todos los compuestos probados. Además, el compuesto 1611-0203 inhibe a Staphylococcus aureus y Enterococcus spp. Los estudios del mecanismo de acción revelan además que 1611-0203 afecta la biosíntesis de la pared celular e inhibe las vías biosintéticas adicionales. Estos resultados combinados indican que los compuestos como el 1611-0203 tienen potencial terapéutico para actuar como anti infecciosos contra varios organismos simultáneamente." @default.
• W2897077180 created "2018-10-26" @default.
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• W2897077180 date "2018-10-11" @default.
• W2897077180 modified "2023-09-23" @default.
• W2897077180 title "Pleiotropic Anti-Infective Effects of Defensin-Derived Antimicrobial Compounds" @default.
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• W2897077180 doi "https://doi.org/10.1637/11912-061118-reg.1" @default.
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