Acyklicke nukleosidy a nukleotidy - antivirotika a cytostatika.

Biologically active derivatives of adenine substituted in the position 9 with hydroxylated aliphatic chain were found to be inhibitors of S-adenosyl-L-homocysteine hydrolase (SAH-hydrolase). The neutral open-chain adenosine analogs are reversible competitive inhibitors of the enzyme while the acid open-chain adenosine analogs are irreversible inhibitors of SAH-hydrolase. Highly effective affinity chromatography ligands derived from 8-hydroxyadenine were also developed. This new approach for purification of SAH-hydrolases permits their simple isolation from crude tissue homogenates. Antimetabolic efficiency of the investigated aliphatic adenosine analogs is due to the cellular SAH-hydrolase inhibition which results in intracellular SAH accumulation and subsequent inhibition of cellular methylases. This mode of antiviral action was documented by viral mRNA undermethylation in vaccinia-virus infected L929 cells, treated with powerful SAH-hydrolase inhibitor AHPA-iBu. The ability of (S)-DHPA to regulate DNA methylations pattern was also proved.The 2nd vol. contains publicated articles in English.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Acyklicke nukleosidy a nukleotidy - antivirotika a cytostatika.

Biologically active derivatives of adenine substituted in the position 9 with hydroxylated aliphatic chain were found to be inhibitors of S-adenosyl-L-homocysteine hydrolase (SAH-hydrolase). The neutral open-chain adenosine analogs are reversible competitive inhibitors of the enzyme while the acid open-chain adenosine analogs are irreversible inhibitors of SAH-hydrolase. Highly effective affinity chromatography ligands derived from 8-hydroxyadenine were also developed. This new approach for purification of SAH-hydrolases permits their simple isolation from crude tissue homogenates. Antimetabolic efficiency of the investigated aliphatic adenosine analogs is due to the cellular SAH-hydrolase inhibition which results in intracellular SAH accumulation and subsequent inhibition of cellular methylases. This mode of antiviral action was documented by viral mRNA undermethylation in vaccinia-virus infected L929 cells, treated with powerful SAH-hydrolase inhibitor AHPA-iBu. The ability of (S)-DHPA to regulate DNA methylations pattern was also proved.The 2nd vol. contains publicated articles in English.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

In Vitro Activities of 3-(Halogenated Phenyl)-5-Acyloxymethyl- 2,5-Dihydrofuran-2-ones against Common and Emerging Yeasts and Molds

Three 3-(halogenated phenyl)-5-acyloxymethyl-2,5-dihydrofuran-2-ones were evaluated for activity against 191 strains of common and emerging yeasts and Aspergillus species by the broth microdilution test performed according to NCCLS guidelines. The furanone derivatives displayed broad-spectrum in vitro activity against potentially pathogenic yeasts and molds, especially Aspergillus spp. (MIC ≤ 2.0 μg/ml) and fluconazole-resistant yeast isolates, including Candida glabrata and Saccharomyces cerevisiae. The 4-bromophenyl derivative was the most effective derivative against the majority of species tested, except for the Candida tropicalis and C. glabrata strains, which were more susceptible to the 3-chlorophenyl derivative. The 3,4-dichlorophenyl derivative possessed a lesser in vitro antifungal effect. The potential of further experiments on animal infection and clinical studies is supported by the relatively low cytotoxicity and acute toxicity of the 4-bromophenyl compound. Thus, the halogenated 3-phenyl-5-acyloxymethyl derivatives of 2,5-dihydrofuran-2-one represent a novel, promising group of compounds with significant activity against relevant opportunistic fungi that are pathogenic to humans