ABSTRACT
INTRODUCTION: Castleman's disease is a rare lymphoproliferative disorder which may be confused with other causes of lymphadenopathy. CASE REPORT: Here we report a case of unicentric Castleman's disease presenting with cervical lymphadenopathy. The patient was treated with complete surgical excision of lesion and was disease free at the time of reporting this article. This case has been reported for its rarity. CONCLUSION: Though castleman's disease is a relatively rare entity it should be strongly considered in the differential diagnosis of cervical lymphadenopathy.
Subject(s)
Anti-Bacterial Agents/chemistry , Osteomyelitis/drug therapy , Prodrugs/chemistry , Rifamycins/chemistry , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/chemical synthesis , Osteomyelitis/prevention & control , Prodrugs/administration & dosage , Prodrugs/chemical synthesis , Rats , Rifamycins/administration & dosage , Rifamycins/chemical synthesis , Staphylococcus aureus/drug effectsABSTRACT
The RNA polymerase holoenzyme is a proven target for antibacterial agents. A high-throughput screening program based on this enzyme from Staphylococcus aureus had previously identified a 2-ureidothiophene-3-carboxylate as a low micromolar inhibitor. An investigation of the relationships between the structures of this class of compounds and their inhibitory- and antibacterial activities is described here, leading to a set of potent RNA polymerase inhibitors with antibacterial activity. Characterization of this bioactivity, including studies of the mechanism of action, is provided, highlighting the power of the reverse chemical genetics approach in providing tools to inhibit the bacterial RNA polymerase.
Subject(s)
Anti-Bacterial Agents/classification , Carboxylic Acids/chemistry , Carboxylic Acids/pharmacology , DNA-Directed RNA Polymerases/antagonists & inhibitors , Drug Resistance, Bacterial , Rifampin/pharmacology , Staphylococcus aureus/drug effects , Thiophenes/chemistry , Thiophenes/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , DNA-Directed RNA Polymerases/metabolism , Molecular Structure , Molecular Weight , Structure-Activity RelationshipABSTRACT
Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , DNA Helicases/antagonists & inhibitors , Triazines/chemistry , Triazines/pharmacology , Amination , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Cell Line , DNA Helicases/metabolism , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/toxicity , Escherichia coli/drug effects , Escherichia coli/enzymology , Humans , Microbial Sensitivity Tests , Molecular Structure , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/enzymology , Staphylococcus aureus/drug effects , Staphylococcus aureus/enzymology , Structure-Activity Relationship , Triazines/chemical synthesis , Triazines/toxicityABSTRACT
The preparation and biological evaluation of 5-substituted-6-hydroxy-2-(anilino)pyrimidinones as a new class of DNA polymerase IIIC inhibitors, required for the replication of chromosomal DNA in Gram-positive bacteria, are described. These new dGTP competitive inhibitors displayed good levels of in vitro inhibition and antibacterial activity against Staphylococcus aureus. A new class of dATP competitive inhibitors, 6-substituted-2-amino-5-alkyl-pyrimidin-4-ones, whose antibacterial activity was unaffected by serum, were identified.
Subject(s)
DNA Polymerase III/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Pyrimidinones/pharmacology , Staphylococcus aureus/enzymology , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Microbial Sensitivity Tests , Molecular Structure , Pyrimidinones/chemical synthesis , Pyrimidinones/chemistry , Staphylococcus aureus/drug effects , Structure-Activity RelationshipABSTRACT
[reaction: see text] The asymmetric synthesis of the methylated tryptophan portion of hemiasterlin peptides is described. The key reactions are a SnCl4-mediated ring opening of epoxynitriles or epoxysulfones by N-methylindole followed by an asymmetric Strecker reaction. A second approach involving opening of glycidic esters by indoles is also described.
