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Biomedical subjects

G Spadoni

Publications and source records attributed to G Spadoni.

34 records · Page 2Linked to original sources
PubMed1990

Structural requirements for inhibitors of poly(ADP-ribose) polymerase.

The purpose of this study was to examine the structure/activity relationships of a series of substituted benzamides as poly(ADP-ribose) polymerase inhibitors. The experimental approach has involved the use of in vitro and in vivo assays in order to gather information either on the intrinsic activity of the benzamides or on the effect of various pharmacodynamic parameters on the activity in vivo. Although some discrepancies between the data obtained in vivo and in vitro were found in this study, results seem to indicate that most powerful inhibitors were characterized by acylation of the -NH2 function in the 3 position or by substitution in this same position with hydroxy or methoxy groups. The best inhibitors were not cytotoxic under these experimental conditions. Computed calculations of molecular electrostatic potential of these molecules were also performed and a good correlation was found between the similarity index and the experimental inhibitory activity.

Benzamides↗
PubMed1990

7-Substituted theophyllines. Part VI--N-[2-(4-chlorophenoxy)-1-phenyl-alkyl]-alkylamido derivatives.

The new amides are inhibitors of cholesterol biosynthesis in vitro as well as in vivo. These compounds are also inhibitors in vivo of triglyceride biosynthesis and of platelet aggregation. All tests showed activity (values expressed as percentage variation) much greater than clofibrate. Besides, all compounds have no effect on coagulation or diuresis and showed low acute toxicity.

Animals↗
PubMed1987

Analogues of benzamide containing a sulfur atom as poly(ADP-ribose) transferase inhibitors.

Structural analogues of benzamide (BA) containing a sulfur atom were tested for their ability to inhibit the enzyme poly(ADP-ribose)transferase (ADPRT) in cultured Chinese Hamster Ovary (CHO) cells. These compounds were benzene sulfonamide (BSA), thiobenzamide (TB) and 3-thiophene carboxamide (TCA) and their activity was compared with that of benzamide in a number of experimental systems. Results have shown that substitution of the carboxamide function with a sulfonamide group produces an almost complete loss of the enzyme inhibiting activity. Also inactive was TB which however was found to display inhibition of the DNA damaging effect of hydrogen peroxide, thus suggesting a hydroxyl radical scavenging effect of TB. TCA, an isostere of BA, produced some inhibition of ADPRT, although its activity was markedly lower than that of the parental drug. Therefore, these results indicate that: 1) ADPRT inhibiting activity is inverse function of dipole moments, hydrogen bonding strength and steric hindrance of the amide functional group and 2) substitution of benzene with thiophene results in a substantial reduction of the enzyme inhibiting activity.

Animals↗
PubMedDate not supplied

3-(2-Carbamoylvinyl)-4,5-dimethylpyrrole-2-carboxylic acids as ligands at the NMDA glycine-binding site: a study on the 2-carbamoylvinyl chain modification.

Twenty 4,5-dimethylpyrrole-2-carboxylic acids (5a-t) with different 2-carbamoylvinyl chains in position 3 were prepared to further investigate the relationships between structure and in vitro affinity for the strychnine-insensitive glycine-binding site. None of these compounds was superior to (E)-3-(N-phenyl-2-carbamoylvinyl)-4,5-dimethylpyrrole-2-carb oxylic acid III (pKi = 6.70), which was taken as a reference standard, but overall the results obtained indicate that the N-phenyl-2-carbamoylvinyl substituent of III may be replaced with the N-(1-adamantyl)-2-carbamoylvinyl group as in 5h (pKi = 6.20) without considerable loss of affinity. This finding adds to previous knowledge.

Animals↗
PubMedDate not supplied

Structure-affinity relationships of indole-based melatonin analogs.

This paper reviews our progress made in characterizing structure-affinity relationships of indole-based melatonin analogs. Evidence is presented suggesting a preferred folded conformation for the amido side chain, almost orthogonal to the plane of indole. A 3D-QSAR comparative molecular field analysis (CoMFA) model, accounting for the observed differences in binding affinity within different classes of melatonergic ligands, and capable of quantitatively predicting the binding affinity of new compounds, is also reported.

Animals↗
PubMedDate not supplied

Indole melatonin agonists and antagonists derived by shifting the melatonin side chain from the C-3 to the N-1 or to the C-2 indole position.

This article reviews our efforts in the development of indole melatonin (MLT) agonist and antagonist compounds. Evidence is presented which indicates that high-affinity melatonergic agonists were obtained by shifting the MLT amido side chain from the C-3 to the N-1 indole position. Conversely, by moving the side chain from the C-3 to the C-2 indole position it is possible to produce MLT antagonist compounds.

Animals↗