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Biomedical subjects

V L Florent'ev

Publications and source records attributed to V L Florent'ev.

At least 19 recordsLinked to original sources
PubMed1993

[Compounds, similar to acyclovir. VIII. Synthesis and antiviral activity of (R/S)-5-hydroxy-4-hydroxymethyl-3-oxapent-2-yl derivatives of nucleic bases].

The (R/S)-5-hydroxy-4-hydroxymethyl-3-oxapent-2-yl derivatives of the uracil, thymidine, cytosine, adenine, guanine and 1,2,4-triazol-3-carboxamide were synthesized using 1,3-diacetoxy-2-(1-acetoxy)propane and 1,3-dichloro-2-(1-chlorethoxy)propane as alkylating agents. The guanine derivatives exhibited activity against HSV-1 (chemotherapeutic index 32).

Acyclovir↗
PubMed1990

[Compounds similar to acyclovir. VII. Attempts to construct an anti-herpetic agent (6-hydroxy-2-oxa-4-hexenyl derivatives of nucleic bases].

Based on the available data on the acyclovir's mechanism of action we attempted to predict the antiherpetic activity of 6-hydroxy-2-oxahexen-4-yl derivatives of nucleic bases. In terms of this model 9-(6-hydroxy-2-oxahexen-4-yl) guanine might be active. 6-Hydroxy-2-oxahexen-4-yl derivatives of adenine, guanine, cytosine, thymine, uracil, 1,2,4-triazole-3 and 1,2,4-triazole-5-carboxamide have been synthesized and their activity against herpes virus I investigated. The guanine derivative proved to possess rather high activity (chemotherapeutical index 8).

Acyclovir↗
PubMed1990

[Compounds similar to acyclovir. VI. Synthesis of optically active 1',2'-seconucleosides].

A convenient method is suggested of synthesis of (3R, 4R)-, (3S, 4S)- and (3R/S, 4S/R)-dihydroxy-3-hydroxymethyl-2-oxapentyl derivatives of the, cytosine, uracyl, adenine and guanine ("full" acyclic analogues of nucleosides with C1'-C2' bond cleaved) by condensation of trimethylsilyl derivatives of nucleic bases (sodium salt in case of adenine) with (3$, 4R)-, (3S )-, (3S, 4S)- and (3R/S, 4S/R)-4,5-diacetoxy-3-acetoxymethyl-1-chloro-2-oxapentanes without catalyst followed by deacetylation.

Acyclovir↗
PubMed1990

[Synthesis, conformation analysis, and antiviral activity of benzimidazole ribofuranosides].

To study the structure-biological effect correlation in the series of nucleoside analogues containing deazapurines, a number of 2-R-benzimidazole 1-beta-D-ribofuranosides (R = H, CF3, SCF3, CH2SCF3, CH2Ph, CH2CN) have been prepared by the modified silyl method. On the basis of CD and PMR data it was shown that the compounds exist in solution mainly as syn-conformers. Calculation of the furanose ring pseudorotation parameters in terms of N-S model indicates the predominance of S-population. In contrast to acyclonucleosides, the ribofuranosides obtained are nonactive against entheroviruses and more cytotoxic.

Antiviral Agents↗
PubMed1987

[Inhibition of influenza virus A RNA-polymerase activity by various 3'-amino-3'-deoxy- and 3'-azido-3'-deoxyribonucleoside-5'-triphosphates].

The effects of 3'-amino-3'-deoxy- and 3'-azido-3'-deoxyribonucleoside-5'-triphosphates on the RNA synthesis catalyzed by influenza virus A RNA polymerase were studied. All nucleotide analogues tested decreased the RNA synthesis twofold at the inhibitor: substrate ratio about 1:5 (in moles). The hypothetic mechanism of inhibitors action based on the incorporation of inhibitors into the 3'-termini of the RNA chains and subsequent blocking of the RNA chains elongation is proposed. The nucleotide analogues under investigation were several times more effective as compared with the ribavirine 5'-triphosphate, a well-known inhibitor of influenza A virus reproduction.

Azides↗
PubMed1986

[Synthesis of acyclic analogs of ribavirin].

A number of ribavirin analogues were prepared in which the ribose moiety was replaced with acyclic substituents imitating some fragments of the ribose ring: 2,3-dihydroxy-prop-1-yl, 3-hydroxymethyl-4-hydroxy-2-oxabut-1-yl, 4,5-dihydroxy-2-oxapent-1-yl and 1,5-dihydroxy-3-oxapent-2-yl. These analogues were synthesized by direct alkylation of ethyl 1,2,4-triazole-3-carboxylate with suitable agents followed by ammonolysis. New convenient methods for preparing the alkylating agents were developed.

Chemical Phenomena↗
PubMed1978

[Substrate specificity of soluble mitochondrial ATPase].

The parameters of the hydrolysis of ATP and several analogs by soluble mitochondrial ATPase were determined. Vmax of the reaction decreases within the range: 2'-desoxy-ATP greater than ATP greater than etheno-ATP greater than GTP greater than 3'-O-methylATP greater than UTP. ATP, 2'-desoxypATP, 3'O-methyl-ATP, GTP, and etheno-ATP are hydrolysed by soluble mitochondrial ATPase with close Km(app) values. CTP is not hydrolysed by the enzyme and does not inhibit the ATPase reaction at a concentration of 10(-2) M. Nucleoside triphosphate derivatives with an "open" ribose cycle 9-[1',5'-dihydroxy-4-(S)-hydroxymethyl-3'-oxapent-2' (R)-yl]adenyl-5'-triphosphate, and 1-[1',5'-dihydroxy-4'-(S)-hydroxymethyl-3'-oxapent-2'(R)-yl[cytosine-5'-triphosphate are effective inhibitors of ATPase (Ki approximately 5.10(-5)M). Mitochondrial ATPase binds the ATP analogs that have hydrocarbon radicals-(CH2)2-, -(CH2)3-, and (CH2)4- instead of the ribose residues: 9-(2'hydroxyethyl)adenyl-2'-triphosphate, 9-(3'-hydroxypropyl)-adenine-3'-triphosphate, and 9-(4'-hydroxybutyl)adenine-4'-triphosphyl)adenine-4'-triphosphate were not hydrolysed by the enzyme, although they inbibit the ATPase reaction (Ki 2.10(-4)M). 9-(2'-hydroxyethyl)adenine-2'-triphosphate is hydrolysed by ATPase eight times more slowly than ATP. It is suggested that the hydrolysis of the substrates of mitochondrial ATPase is- preceded by the binding of the substrates in a tense conformation in the active site of the enzyme.

Adenosine Triphosphatases↗
PubMed1976

[Inhibition of pyridoxal kinase by 2- and 6-alkyl substituted vitamin B6 analogues and by pyridoxal oximes].

It is shown in the system with partially purified pyridoxal kinase from mouse liver, that the presence of one alkyl group in the 2nd or 6th positions of pyridine cycle in pyridoxole and pyridoxamine derivatives and pyridoxal oximes is a necessary condition which determines relatively high affinity of structural vitamin B6 analogues to the enzyme. 2'-n-Propylpyridoxal was phosphorylated by pyridoxal kinase with a relatively high rate, while 2-nor-6-methylpyridoxal, having a similar affinity to pyridoxal kinase, was not phosphorylated at all. The data obtained indicate an important role of the methyl group in the 2nd position of pyridine cycle in vitamin B6 molecule for its fixation in the enzyme active site and for the proper orientation, which provides enzymatic substrate phosphorylation. Some structural peculiarities of vitamin B6 analogues are considered, pre-determining their low or high efficiency as vitamin B6 antimetabolite in vivo.

Animals↗
PubMed1976

[Interaction of 4-aminobutyrate-transaminase from swine kidneys with 5'- and 6'-methyl derivatives of pyridoxal-5'-phosphate].

The study of interaction of 4-aminobutyrate transaminase with 5'- 6'-methyl derivates of PLP demonstrated that only the former was capable of forming a catalytically active holoenzyme possessing 0.37 activity of the native holoenzyme and a low affinity substrates. This compound interacts with the apoenzyme at a slower rate than does PLP; it has a reduced affinity towards apotransaminase (Km = 1.10(-4) M) and is replaced from the active site by native coenzyme. The other analog of pyridoxal-5'-phosphate forms a catalytically inactive complex with the apoenzyme; the other analog is not replaced from the active center by native coenzyme and non-competitively inhibits the reconstruction of apotransaminase (Ki = 2.10(-5) M).

4-Aminobutyrate Transaminase↗
PubMedDate not supplied

[Theoretical study of the structure of adenosine deaminase complexes with adenosine analogues: I. Aza-, deaza- and isomeric azadeazaanalogues of adenosine].

The conformational models of the active site of adenosine deaminase (ADA) and its complexes in the basic state with adenosine and 13 isosteric analogues of the aza, deaza, and azadeaza series were constructed. The optimization of the conformational energy of the active site and the nucleoside bound with it in the complex was achieved in the force field of the whole enzyme (the 1ADD structure was used) within the molecular mechanics model using the AMBER 99 potentials. The stable conformational states of each of the complexes, as well as the optimal conformation of the ADA in the absence of ligand, were determined. It was proved that the conformational state that is close to the structure of the ADA complex with 1-deazaadenosine (1ADD) known from the X-ray study corresponds to one of the local minima of the potential surface. Another, a significantly deeper minimum was determined; it differs from the first minimum by the mutual orientation of side chains of amino acid residues. A similar conformational state is optimal for the ADA active site in the absence of the bound ligand. A qualitative correlation exists between the values of potential energies of the complexes in this conformation and the enzymatic activity of ADA toward the corresponding nucleosides. The dynamics of conformational conversions of the active site after the binding of substrate or its analogues, as well as the possibility of the estimation of the inhibitory properties of nucleosides on the basis of calculations, are discussed.

Adenosine↗
PubMedDate not supplied

[Theoretical study of antagonists and inhibitors of mammalian adenosine deaminase. I. Adenosine and its aza- and deaza-analogs].

Aza- and deazaanalogues of adenosine, including their 1-protonated forms (except for that of 1-deazaadenosine), were studied by computer computation to find a relationship between their molecular structures and substrate properties for the mammalian adenosine deaminase. The atomic charge distribution and maps of the electrostatic potential around their van der Waals molecular surface were calculated for these compounds using the ab initio STO-3G method. The conformational studies were carried out by the MM+ method of molecular mechanics. The mechanism that determines the substrate selectivity of mammalian adenosine deaminase is discussed. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2002, vol. 28, no. 4; see also http://www.maik.ru.

Adenosine↗