Showing papers by "Zygmunt Kazimierczuk published in 1999"

Antimicrobial activity of substituted azoles and their nucleosides.

Abstract: Four new 2'-deoxynucleosides of benzimidazole derivatives were prepared. Antimicrobial activity of many indazole, benzotriazole, benzimidazole derivatives and their nucleosides were tested by the agar diffusion method. Among the investigated compounds, dinitro- and trifluoromethyl-substituted benzimidazoles and their nucleosides were the most potent.

Studies on the Adamantylation of N‐Heterocycles and Nucleosides

Abstract: Adamantylation of several N-heterocycles and of two ribonucleosides (uridine and toyocamycin) was studied. The exact substitution position by the adamantyl carbocation generated from adamantan-1-ol in CF3COOH depends on the nature of the heterocyclic substrate. Thus, adamantylation of an additional exocyclic amino group (see Scheme 1), N-adamantylation of the heterocycle (Scheme 2), C-adamantylation of the heterocycle (Scheme 3), as well as the formation of heterocyclic N-adamantylcarboxamides via the Ritter reaction (Scheme 4) are possible. The structures of the reaction products were determined by means of elemental analysis and NMR, UV, and IR spectroscopy.

Synthesis of 6-aryloxy- and 6-arylalkoxy-2-chloropurines and their interactions with purine nucleoside phosphorylase from Escherichia coli.

Abstract: The phase transfer method was applied to perform the nucleophilic substitution of 2,6-dichloropurines by modified arylalkyl alcohol or phenols. Since under these conditions only the 6-halogen is exchanged, this method gives 2-chloro-6-aryloxy- and 2-chloro-6-arylalkoxy-purines. 2-Chloro-6-benzylthiopurine was synthesized by alkylation of 2-chloro-6-thiopurine with benzyl bromide. The stereoisomers of 2-chloro-6-(1-phenyl-1-ethoxy)purine were obtained from R- and S-enantiomers of sec.-phenylethylalcohol and 2,6-dichloropurine. All derivatives were tested for inhibition with purified hexameric E. coli purine nucleoside phosphorylase (PNP). For analogues showing IC50 12 microM). More rigid (e.g. phenoxy-), non-planar (cyclohexyloxy-), or more bulky (2,4,6-trimethylphenoxy-) substituents at position 6 of the purine base gave less potent inhibitors (IC50 = 26, 56 and > 100 microM, respectively). The derivatives are selective inhibitors of hexameric "high-molecular mass" PNPs because no inhibitory activity vs. trimeric Cellulomonas sp. PNP was detected. By establishing the ligand-dependent stabilization pattern of the E. coli PNP it was shown that the new derivatives, similarly as the natural purine bases, are able to form a dead-end ternary complex with the enzyme and orthophosphate. It was also shown that the derivatives are substrates in the reverse synthetic direction catalyzed by E. coli PNP.