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M Recanatini

Publications and source records attributed to M Recanatini.

At least 37 records · Page 2Linked to original sources
PubMed1998

Comparative molecular field analysis of non-steroidal aromatase inhibitors: an extended model for two different structural classes.

Aromatase is a cytochrome P450 isozyme, whose inhibition is known to be therapeutically relevant in the treatment of the breast cancer. A comparative molecular field analysis (CoMFA) has been carried out on a series of non-steroidal aromatase inhibitors belonging to two different structural classes. One subset of compounds consists of fadrozole analogues and was studied in a previous work, from which a 'local' 3-D quantitative structure-activity relationship (QSAR) model for the inhibition of aromatase was obtained. In the present paper, that model is extended to include a second subset of compounds bearing a tetralone nucleus and acting at the same enzyme site with the same mechanism as the azoles. The critical alignment step has been solved by using two different steroidal inhibitors of aromatase as rigid templates, on which the non-steroidal compounds have been superimposed. The final 3-D QSAR models are discussed in terms of predictivity and some implications regarding the steric and electronic requirements of steroidal and non-steroidal inhibitors are pointed out.

Aromatase Inhibitors↗
PubMed1997

A comparative QSAR analysis of acetylcholinesterase inhibitors currently studied for the treatment of Alzheimer's disease.

Considering the relevance of acetylcholinesterase inhibitors as potential agents for the treatment of the Alzheimer's disease, we have undertaken a comparative QSAR analysis aimed at individuating the physico-chemical properties governing the inhibitory activity of such compounds. The QSAR equations for 13 series of derivatives have been calculated and discussed. The series studied are all those we found in the literature suitable for a QSAR analysis and represent the three main classes of acetylcholinesterase inhibitors currently investigated, namely, physostigmine analogues, 1,2,3,4-tetrahydroacridines and benzylamines. The equations we obtained show that, within each class, the main physico-chemical properties affecting the inhibitory activity are almost the same for all the series and can be individuated by the use of proper parameters. The conclusions of this study can be summarized as follows: (a) hydrophobicity plays a critical role in both the physostigmine- and the benzylamine-derived classes; (b) electronic effects are important for the interactions carried out by the variable portion of benzylamine derivatives; and (c) steric factors are also significant, but, as in other cases, the collinearity between steric and hydrophobic parameters does not allow one to draw any final conclusion.

Acetylcholinesterase↗
PubMed1997

Synthesis, cytotoxicity and SAR of simple geiparvarin analogues.

Some simple geiparvarin analogues, in which the coumarin moiety has been replaced with an X-substituted benzene ring, are described. The compounds were tested on LoVo cells (human colon carcinoma cell line) and some of them show a cytotoxicity comparable with that of the prototype. A QSAR analysis was also attempted, but it did not provide satisfactory results, mainly because of the limited range of variation of the biological activity.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Comparative molecular field analysis of non-steroidal aromatase inhibitors related to fadrozole.

A series of non-steroidal inhibitors of aromatase, structurally related to fadrozole (2), was investigated with the aim of developing a 3D QSAR model using the Comparative Molecular Field Analysis (CoMFA) technique. The alignment of the molecules was performed following two approaches (atom-by-atom and field fit), both starting from an initial hypothesis of superimposition of fadrozole to a steroidal inhibitor (3). From a number of CoMFA models built with different characteristics, one was recognized as the most statistically relevant; this one is discussed in detail. The features of the 3D QSAR model are consistent with those of other 3D and QSAR models of aromatase and its inhibitors.

Aromatase Inhibitors↗
PubMed1995

Synthesis, muscarinic blocking activity and molecular modeling studies of 4-DAMP-related compounds.

A number of compounds structurally related to 4-DAMP (1) were synthesized and a single crystal X-ray structural study on a representative member of this series was carried out. All the compounds were tested for the antagonist activity in isolated guinea pig atria (M2 muscarinic receptors) and ileum (M3 muscarinic receptors). Affinity values (pA2) for the muscarinic receptor subtypes ranged from 5.39 to 9.71 (M2) and from 5.68 to 9.92 (M3), depending on different structural features of the compounds. A molecular modeling study was performed, with the aim of rationalizing the affinity data for both M2 and M3 muscarinic receptor subtypes. The presence in the series of two highly active, structurally constrained derivatives allowed us to define two different pharmacophoric frames on which all the compounds could be fitted in a satisfactory manner.

Animals↗
PubMed1992

Partition and distribution coefficients of aryloxypropanolamine beta-adrenoceptor antagonists.

n-Octanol/water partition and distribution coefficients of fifteen beta-blockers have been measured and the relationships between log P (neutral species), log Pi (fully ionized species) and log D7.4 have been examined. A strict correlation exists among these three parameters, suggesting that the ionization exerts similar effects on the partition behaviour of these drugs.

Adrenergic beta-Antagonists↗
PubMed1991

Synthesis, antibacterial activity and structure-activity relationships of N-substituted 4-diazo-pyrazole-5-carboxamides. 2.

A series of 4-diazopyrazole-5-carboxamides 1 d-n has been synthesized and their antibacterial activity against a number of Gram-negative and Gram-positive strains has been tested. Some of the compounds resulted quite active and the whole set allowed to further study the SAR of the class. Substituents in position 5 affect Gram-negative and Gram-positive activities via bulk and electronic properties respectively; position 3 mostly affects the Gram-negative activity, while the presence of the charged diazo group in position 4 is crucial for both antibacterial activities.

Amides↗
PubMed1989

Synthesis and quantitative structure-activity relationships of analeptic agents related to dimefline.

Some new dimefline-type derivatives have been synthesized and their pharmacological activity, as well as their distribution coefficients have been determined. The distribution coefficients of a number of previously published analogue compounds have also been measured and the QSAR analysis of the whole set has been carried out. The results of such analysis allow to point out which factors are influencing the biological activity of this group of compounds.

Animals↗
PubMed1989

Synthesis, antibacterial activity and structure-activity relationships of N-substituted 3-methyl-4-diazo-5-pyrazolecarboxamides.

A number of N-substituted 3-methyl-4-diazo-5-pyrazolecarboxamides (IVa-p) have been synthesized and tested for their in vitro antibacterial activity. All the compounds have been assayed against several representative Gram-negative and Gram-positive bacteria, as well as against some intestinal bacterial species. Some of the 4-diazopyrazoles IVa-c have shown a quite interesting broad-spectrum activity, while they are ineffective against the "protective" intestinal flora. The structure-activity relationships of the series have been studied quantitatively, via both univariate and multivariate methods: the results are consistent and permit some rationalization of the behaviour of the compounds investigated.

Anti-Bacterial Agents↗
PubMed1987

Chymotrypsin hydrolysis of X-phenyl hippurates. A quantitative structure-activity relationship and molecular graphics analysis.

The hydrolysis of a set of 28 X-phenyl hippurates by chymotrypsin was investigated. From the derived Km and kcat values a quantitative structure-activity relationship was developed. This equation shows that para substituents correlated by sigma- display only an electronic effect on the formation of the ES complex whereas meta hydrophobic substituents show a hydrophobic interaction correlated by pi in addition to their electronic effect. Meta polar substituents avoid contact with the enzyme and show only electronic effects on Km. Using the x-ray crystallographic coordinates for chymotrypsin and computer graphics, a model was constructed which is used to interpret the quantitative structure-activity relationship. As with a number of previously reported examples, we have found that when polar substituents have the option of binding to hydrophobic space or remaining in the aqueous phase they follow the latter possibility.

Binding Sites↗
PubMed1987

Concanavalin X-phenyl beta-D-glucopyranoside interactions. A molecular graphics-QSAR analysis.

Poretz and Goldstein showed that X-phenyl beta-D-glucopyranosides prevent the agglutination of concanavalin A with polysaccharides and derived inhibition constants for the process. Using their data the binding of 25 glucosides to concanavalin is now shown to be correlated with the molar refractivity of the substituents on the phenyl ring. This is interpreted to mean that it is the bulk of the substituents and not their hydrophobicity which prevents the union of concanavalin and the polysaccharide. These results are similar to those found for other haptens preventing antibody-antigen interaction.

Concanavalin A↗
PubMed1986

Quantitative structure-activity relationships and molecular graphics in ligand receptor interactions: amidine inhibition of trypsin.

Quantitative structure-activity relationships have been formulated for four sets of amidine inhibitors of trypsin. The quantitative results from these equations are compared with qualitative models constructed from the X-ray crystallographic coordinates of a benzamidine bound to trypsin. The good agreement between the mathematical and graphics models provides further support for the use of substituent constants and regression analysis in the study of enzyme-ligand interactions.

Amidines↗