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Biomedical subjects

L Fontanella

Publications and source records attributed to L Fontanella.

At least 19 recordsLinked to original sources
PubMed1999

Characterization and properties of dominant-negative mutants of the ras-specific guanine nucleotide exchange factor CDC25(Mm).

Ras proteins are small GTPases playing a pivotal role in cell proliferation and differentiation. Their activation depends on the competing action of GTPase activating proteins and guanine nucleotide exchange factors (GEF). The properties of two dominant-negative mutants within the catalytic domains of the ras-specific GEF, CDC25(Mm), are described. In vitro, the mutant GEF(W1056E) and GEF(T1184E) proteins are catalytically inactive, are able to efficiently displace wild-type GEF from p21(ras), and strongly reduce affinity of the nucleotide-free ras x GEF complex for the incoming nucleotide, thus resulting in the formation of a stable ras.GEF binary complex. Consistent with their in vitro properties, the two mutant GEFs bring about a dramatic reduction in ras-dependent fos-luciferase activity in mouse fibroblasts. The stable ectopic expression of the GEF(W1056E) mutant in smooth muscle cells effectively reduced growth rate and DNA synthesis with no detectable morphological changes.

Animals↗
PubMed1999

Photometric assay for polynucleotide phosphorylase.

Polynucleotide phosphorylase (PNPase) is a prokaryotic enzyme that catalyzes phosphorolysis of polynucleotides with release of NDPs. It is also believed to play a key role in turnover of prokaryotic transcripts, thus regulating gene expression. At the moment, only radioisotopic methods are available for assaying PNPase in crude extracts; these involve incubating [32P]phosphate and poly(A) in the presence of the enzyme, separating [32P]phosphate from [32P]ADP, and quantifying ADP by scintillation counting. Photometric assay using pyruvate kinase and lactate dehydrogenase as auxiliary enzymes is not feasible in crude extracts because of endogenous ATPase activities, which regenerate ADP from the ATP released by pyruvate kinase. Here, we present a simple photometric assay that uses a cyclic detection system which, due to the sequential action of pyruvate kinase and hexokinase, results in an exponential increase of ADP and glucose 6-phosphate. Glucose 6-phosphate is then revealed by a glucose-6-phosphate dehydrogenase reaction. Based on the theoretical model, a linear increase in absorbance is predicted as a function of the square of the reaction time, with a slope proportional to PNPase activity. Experimental data confirmed the theoretical predictions and showed that the assay was quantitative and unquestionably specific. We also devised a simple procedure for determining absolute enzyme activities (expressed in micromoles of product formed per minute) using exact amounts of pure PNPase as internal standards.

Adenosine Diphosphate↗
PubMed1984

[Derivatives of 2,3,5,6,7,7a-hexahydro-1,3-dioxo-1H-pyrrolo[1,2-c]imidazol -5-carboxylic acids].

The synthesis of the above-mentioned compounds, starting from the diethyl ester of 2,5-pyrrolidine dicarboxylic acid, is reported. The cis and trans isomers od the 2-phenylsubstituted acid were separated, and the trans form was resolved into the two chiral forms. Some amides were also prepared from these acids. The thio analogs (XIII) and (XVI) and the partially reduced derivatives (XIV) were synthesized. Some amides (VI) showed an interesting anti-anxiety effect in pharmacological models.

Animals↗
PubMed1984

[Substances with central nervous system activity. Derivatives of octahydro-1,4-dihydroxypyrrolo(1,2-a)pyrazine-6-carboxylic acids].

Compounds with potential activity on the Central Nervous System were prepared starting either from 2,5-diethoxycarbonylpyrrolidine or from N-benzyloxycarbonyl-2,5-pyrrolidinedicarboxylic acid anhydride. By the Arndt-Eistert reaction it was possible to obtain chain lengthening at position 6. The carboxy group was also successfully reduced to a hydroxymethyl group. The synthetic work was completed with the synthesis of some derivatives having a phenyl ring condensed at position 7 and 8. Some pharmacological data on the Central Nervous System depressant activity of the prepared compounds are also reported.

Aggression↗
PubMed1981

Synthesis of new psychotropic 2-imidazolidinones.

The report describes the synthesis and pharmacology of some new derivatives of 1-(m or p-chlorophenyl)-2-imidazolidinone. These compounds were obtained either by reacting an amine with an N-(2-chloroethyl)-2-imidazolidinone or by reacting a 2-chloroethylamine with an N-substituted-2-imidazolidinone. Two compounds (II f, h) showed interesting psychotropic activity.

Animals↗
PubMed1978

[Tricyclic homologs of piperazine. III. Synthesis of 4-substituted hexahydro-1H-2,6-methanopyrrolo[1,2a]pyrazines].

The Authors describe the synthesis of some quaternary salts of the hexahydro-1H-2,6-methanopyrrolo[1,2-a]pyrazines mono or disubstituted at carbon-4. These were obtained directly by cyclization of the corresponding diazabicyclooctanes, by formation of a substituted ethylenic bridge between the two nitrogen atoms. The compounds were pharmacologically screened; the hypothesis of enhancement of curare-like activity in comparison with the unsubstituted derivatives was not confirmed.

Animals↗
PubMed1978

[Bicyclic piperazine homologues XIV (1). Synthesis and analgesic activity of 3,8-diaza-bicyclo[3.2.1.] octane derivatives].

The synthesis of two new series of 3,8-diazabicyclo [3.2.1] octane derivatives is described. The first series includes some 3-(or 8)-allyl and 3-(or 8)-(3,3-dimethylallyl) derivatives of 3,8-diazabicyclo [3.2.1] octane and 3,8-diazabicyclo [3.2.1] octane-2-one. The second series includes some esters and carbamates of 3-(3-hydroxy-3-methyl)butyl-3,8-diazabicyclo [3.2.1] octane. Two new 3,8-diazabicyclo [3.2.1] octane derivatives structurally related to propoxyphene are also described. Some pharmacological data of these compounds are reported.

Analgesics↗
PubMed1977

[Bicyclic analogs of piperazine. XII. (1) - Synthesis of 3,8-diazabicyclo/3,2,1/octanes as potential antiparkinson agents].

As a part of research on 3,8-diazabicyclo [3,2,1] octanes, the Authors report on the synthesis of some amides of methyl, phenyl and cyclohexyltropic acid, potentially active as antiparkinson agents. Also reported is the synthesis of some compounds similar to two known drugs, Caramiphene and Cycrimine. These compounds differ from the said drugs in having a 3,8-diazabicyclo [3,2,1] octane as a basic moiety.

Antiparkinson Agents↗
PubMed1975

[Bicyclic analogs of piperazine. XIII (1). Derivatives of 3,8-diazabicyclo[3.2.1]octane with potential anti-inflammatory activity].

The Authors describe the synthesis of some 8-acyl-3-methyl-3,8-diazabicyclo[3.2.1]octanes and 3-acyl-8-methyl-3,8-diazabicylo[3.2.1] octanes. The compounds were prepared by acylation of the corresponding methyl derivatives with the purpose of obtaining antiinflammatory compounds. The synthesis of some 3-alkyl-8-propionyl-3,8-diazabicylo[3.2.1]octanes is also described. These compounds were prepared in analogy with some 8-pripionyl-3,8-diazabicyclo[3.2.1]octanes endowed with high analgesic and antiinflammatory activity.

Anti-Inflammatory Agents↗
PubMed1975

[Synthesis of 1-and 3-phenyl substituted 1,5-dihydro-2,4-benzoxazepin-3(4H)-ones].

The synthesis of 1-phenyl-1,5-dihydro-2,4-benzoxazepin-3(4H)-ones (II), of 5-phenyl-1,5-dihydro-2,4-benzoxazepin-3(4H)-ones (III) and of the 7-chloro substituted analogs is described. These compounds were prepared by reacting the corresponding amino alcohols with COCl2 in the presence of Na2CO3. The reactivity of some compounds of this series in acid or basic media is also described.

Amino Alcohols↗