ABSTRACT
Casualties caused by nerve agents, potent acetylcholinesterase inhibitors, have attracted attention from media recently. Poisoning with these chemicals may be fatal if not correctly addressed. Therefore, research on novel antidotes is clearly warranted. Pyridinium oximes are the only clinically available compounds, but poor penetration into the blood-brain barrier hampers efficient enzyme reactivation at the central nervous system. In searching for structural factors that may be explored in SAR studies, we synthesized and evaluated neutral aryloximes as reactivators for acetylcholinesterase inhibited by NEMP, a VX surrogate. Although few tested compounds reached comparable reactivation results with clinical standards, they may be considered as leads for further optimization.
Subject(s)
Acetylcholinesterase/metabolism , Cholinesterase Reactivators/chemical synthesis , Oximes/chemistry , Pyrrolidines/chemistry , Acetylcholinesterase/chemistry , Animals , Antidotes/chemical synthesis , Antidotes/metabolism , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/metabolism , Cholinesterase Reactivators/metabolism , Eels , Organothiophosphorus Compounds/chemistry , Organothiophosphorus Compounds/metabolism , Oximes/metabolism , Pyrrolidines/metabolism , Structure-Activity RelationshipABSTRACT
Group B streptococci (GBS) infections occur worldwide. Although serotyping has been used for epidemiologic purposes, this does not accurately characterize enough members of a genetically heterogeneous bacterial population. The aims of this work were to evaluate the genetic diversity of 45 type Ia GBS strains isolated in Brazil by pulsed-field gel electrophoresis as well as to evaluate antimicrobial susceptibility profiles and identify virulence genes. Twenty-four strains were assigned to cluster A. All strains under study contained the hylB and scpB genes. The bca gene was detected in only 10 strains and none of the streptococci carried the bac gene. Thirty-nine strains were resistant to tetracycline.
Subject(s)
Anti-Bacterial Agents/pharmacology , DNA, Viral/analysis , Genes, Viral/genetics , Streptococcus agalactiae , Brazil , Disk Diffusion Antimicrobial Tests , Electrophoresis, Gel, Pulsed-Field , Genetic Variation , Humans , Streptococcus agalactiae/drug effects , Streptococcus agalactiae/genetics , Streptococcus agalactiae/pathogenicity , Virulence/geneticsABSTRACT
Group B streptococci (GBS) infections occur worldwide. Although serotyping has been used for epidemiologic purposes, this does not accurately characterize enough members of a genetically heterogeneous bacterial population. The aims of this work were to evaluate the genetic diversity of 45 type Ia GBS strains isolated in Brazil by pulsed-field gel electrophoresis as well as to evaluate antimicrobial susceptibility profiles and identify virulence genes. Twenty-four strains were assigned to cluster A. All strains under study contained the hylB and scpB genes. The bca gene was detected in only 10 strains and none of the streptococci carried the bac gene. Thirty-nine strains were resistant to tetracycline.
