Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0519030 (Klebsiella)
 21,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tilivalline (1a), a metabolite isolated from Klebsiella pneumoniae var. oxytoca, belongs to a group of pyrrolo[2,1-c][1,4]benzodiazepines, a characteristic skeleton of anthramycin-type antitumor antibiotics. We have accomplished a completely stereoselective, efficient and convenient synthesis of 1a utilizing a new Mannich type intramolecular cyclization as a key step. Further, a computational chemical analysis clarified the effect of zinc chloride on the high stereoselectivity in the tilivalline synthesis. To aim both the extension of the scope of the new Mannich type intramolecular cyclization and the studies on the structure-biological activity relationship, we further extended the method to the synthesis of tilivalline derivatives and 2-(3'-indolyl)-1,4-benzodiazepines (50). Investigation on the cytotoxicity of 1a and its analogs has revealed that 1a shows the strong cytotoxicity toward mouse leukemia L 1210 cells and the replacement of the indole function of 1a with cyano one increases the cytotoxicity of 1a about 100 times (IC50 = 0.05 microgram/ml).
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PMID:[A stereoselective synthesis of tilivalline and its analogs utilizing a new Mannich type intramolecular cyclization]. 766 57

Prompt empiric antibiotic therapy is of critical importance for patients with neutropenic fever. However, a major concern with important clinical consequences is the emergence of bacterial resistance to antibiotics. After using ceftazidime with a glycopeptide as initial empiric therapy for neutropenic fever, we were confronted with a 75% reduced susceptibility rate to ceftazidime of inducible Enterobacteriaceae collected in 1994. The initial empiric therapy was therefore replaced in May 1995 by a combination of cefepime with amikacin, with addition of a glycopeptide after 48 h if necessary. After this change, we observed a significant decrease in reduced susceptibility of inducible Enterobacteriaceae, not only to ceftazidime, but also to amikacin, cotrimoxazole and ciprofloxacin. There was also a decrease in reduced susceptibility of non-inducible Enterobacteriaceae, such as Klebsiella spp, to ceftazidime. The reduction of resistance may be related at least in part to the combined use of cefepime together with an aminoglycoside. This study shows that it is possible to reverse bacterial resistance by modifying the antibiotic regimen used.
Leukemia 1998 Oct
PMID:Decreasing antibiotic resistance of Enterobacteriaceae by introducing a new antibiotic combination therapy for neutropenic fever patients. 976 9