Phosphonopeptides as Antibacterial Agents: Alaphosphin and Related Phosphonopeptides
AUTOR(ES)
Allen, John G.
RESUMO
Alaphosphin, l-alanyl-l-1-aminoethylphosphonic acid, was selected from a range of phosphonopeptides for evaluation in humans on the basis of its antibacterial activity, pharmacokinetics, and stability to intestinal and kidney peptidases. In vitro, the antibacterial action was antagonized by small peptides, resulting in low activity on peptone media. On an antagonist-free medium alaphosphin was bactericidal and rapidly lysed most susceptible gram-negative bacteria, but it was largely bacteriostatic and essentially nonlytic against gram-positive organisms. Its spectrum included most strains normally isolated from urinary tract infections, but potency was greatly reduced by very high inoculum levels and by alkaline pH. Although strains of Proteus and Pseudomonas were less susceptible to alaphosphin than were other common gram-negative bacteria, like other species they formed spheroplasts when exposed under appropriate conditions. Alaphosphin was equally effective against penicillin-susceptible and -resistant strains and showed no cross-resistance with known antibiotics. Good synergy and increased bactericidal activity were demonstrated with combinations of alaphosphin and d-cycloserine or β-lactam antibiotics.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=352739Documentos Relacionados
- Phosphonopeptides as Antibacterial Agents: Mechanism of Action of Alaphosphin
- Phosphonopeptides as Antibacterial Agents: Rationale, Chemistry, and Structure-Activity Relationships
- Phosphonopeptides as antibacterial agents: metabolism and pharmacokinetics of alafosfalin in animals and humans.
- Boron-containing antibacterial agents: effects on growth and morphology of bacteria under various culture conditions.
- Polysaccharide Immunomodulators as Therapeutic Agents: Structural Aspects and Biologic Function