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C Silipo

Publications and source records attributed to C Silipo.

At least 37 records · Page 2Linked to original sources
PubMed1981

OSAR in a series of muscarinic agents. Note III--Alkyltrimethylammonium salts, ethers and esters of choline.

In the light of the experience gained studying various sets of muscarinic ligands related to a rigid model, flexible structures such as alkyltrimethylammonium salts, ethers and esters of choline have been prepared and their affinities (pD2) have been studied. The quantitative structure-activity relationships (QSAR) show that the pD2 value is strongly dependent on hydrophobic and steric parameters of the ligand substituent. Moreover, two indicator variables are considered to take ito account extra-activities connected with ligand special structural features. The overall QSAR confirm that the electrostatic attraction, the hydrophobic bonding and the polar interaction holding the ligand on the receptor are individually weak; however, these three forces collectively permit a more complete utilization of the receptor binding site.

Animals↗
PubMed1980

QSAR in a series of muscarinic agents. Note II - Pyridine and furan derivatives.

Two sets of substantial picolyl and furfuryltrimethylammonium salts have been synthesized and their affinities (expressed as pD2) have been studied with the aim of characterizing muscarinic receptor spaces to which the ligand structural features bind. The new data were combined with those relative to a set of substituted benzyltrimethylammonium salts previously studied to formulate an overall QSAR which showed that the pD2 value is strongly dependent on hydrophobic and steric parameters of the ring substituent. Moreover, two indicator variables were considered to take into account the extra-activity associated with special structural features of the heterocyclic system and the further increase in activity associated with a "cooperative interaction" between the lipophilic binding of the substituent and a polar interaction of the ring heteroatom. The results confirm our earlier predictions and offer a model for ligand binding which gives a consistent view of the topology of the ligand attachment points on the receptor.

Animals↗
PubMed1979

[Analysis of phenothiazine neuroleptics by means of non-aqueous titrimetry].

Phenothiazine neuroleptic drugs, either as pure compounds or in pharmaceutical dosage forms have been quantitatively assayed by nonaqueous titrimetry. Suggested procedure is applicable to basic drugs and their corresponding salts without prior cleanup overcoming the interferences due to excipients.

Antipsychotic Agents↗
PubMed1979

A reanalysis of the structure-activity relationships of sulfonamide derivatives.

A reanalysis of correspondence between electronic distribution of sulfonamides and their antibacterial activity is proposed. Correlation equations show that the rate limiting steps for sulfonamide action on E. coli cell-free system and whole cell system have similar dependence on the negative logarithm of the ionization constant. The existence of a "bilinear relationship" demonstrates that the whole class of compounds has a single mechanism of action and that permeability factors are unimportant in both biological processes.

Escherichia coli↗
PubMed1979

QSAR in a series of muscarinic agents.

The results of a pharmacological investigation on a series of 3-substituted benzyltrimethylammonium salts possessing muscarinic activity are reported. Correlative analysis shows that the pharmacodynamic activity is a function of the hydrophobic-lipophilic and steric parameters associated with the substituents. In particular, it is revealed that a lipophilic pocket of limited size is present in the muscarinic receptor at an optimal distance from the electron--rich site with which the cationic termination interacts.

Animals↗
PubMed1979

QSAR of the inhibition of glyoxalase by S-substituted glutathiones.

A quantitative structure-activity relationship (QSAR) has been formulated for the inhibition of glyoxalase I from yeast by 37 S-substituted glutathiones: log 1/C = 1.23 pi' + 1.20 MR4 - 0.67 I1 - 0.14 pi'2 + 1.85 C in this expression is the molar concentration of inhibitor producing 50% inhibition, pi' is the usual hydrophobic parameter modified for certain substituents, MR4 is the molar refractivity of certain p-phenyl substituents, and I1 is an indicator variable for those congeners with an acetylated alpha-amino group. This equation should be of help in the design of more effective inhibitors which may be of value in cancer chemotherapy.

Chemical Phenomena↗
PubMed1979

Physicochemical parameters in biological correlation analysis: meaning and limits.

Correlation analysis assumes that the physicochemical factors governing the transport, metabolism and drug-receptor interaction can be factored into hydrophobic-lipophilic component, polarizability and dispersion forces, electronic and steric effects and into indeterminate factors. Using computerized regression analysis, a generalized equation can be formulated to correlate the biological response of a set of compounds with their chemical structures in terms of physicochemical parameters of substituents. In order to explore the scope of each defined physicochemical parameter, correlations between biological effects and some combination of substituent indices are discussed.

Chemical Phenomena↗
PubMed1978

[Correlative analysis in the study of enzyme-ligand interactions].

A comprehensive study on enzyme ligand interactions by QSAR techniques is discussed. Thirteen correlation equations are presented which relate activity of 1086 ligands of isolated chloroplasts, chymotrypsin, dihydrofolate reductase, xanthine oxidase and guanine deaminase to their chemical structures. Two kinds of space within and on the surface of an enzyme are defined by means of pi and MR constants. Emphasis is put on the use of indicator variables as a means of rationalizing special enzyme-ligand interactions. The use of such studies for drug development is discussed.

Chloroplasts↗
PubMed1978

[Benzotriazole derivatives active on plant growth. I. Preparation, characterization, and correlation between physicochemical properties and structure].

Following preliminary observations of auxin-like activity for several benzotriazole derivatives, a large number of new derivatives bearing on position 1 or 2 different kinds of omega-substituted chains were prepared and tested for activity on plant growth. Some physico-chemical properties which are potentially correlated with biological activity were determined for all the new benzotriazole derivatives and for those already studied in this field as growth promoting substances. Partition coefficients (between n-octanol and buffer with pH 5.6) and RM values of 2-substituted isomers were correlated, through regressional analysis, with the corresponding properties of 1-substituted isomers. Finally, the chromatographic characterictics of the sixty substances so far considered were correlated, again through regressional analysis, with the corresponding partition coefficients and with structural features and specific functional groups by which the eventual interactions with the substratum are regulated.

Chemical Phenomena↗
PubMed1978

[Effect of benzotriazole derivatives on plant growth. II].

The action on plant growth of sixty benzotriazole derivatives carrying on position 1 or 2 several kinds of substituents, has been studied via the oat coleoptile section elongation test. At medium and low concentrations almost all compounds behave as activators, while at the highest concentrations many of them, like indolylacetic acid (IAA), are growth inhibitors. It is worth noting the lack of toxicity, even at the highest concentration used, for the 1-hydroxyalkylbenzotriazoles and, more generally speaking, the low toxicity of hydroxyalkylbenzotriazoles and of benzotriazolylalkanoic acid amides. In the range of concentration from 10(-6) to 10(-8) M some methylalkylbenzotriazoles as well as some benzotriazolylalkanoic acids and esters are more active than IAA exhibiting from 40 to 60% of the maximal activity of IAA. The activities of methylalkylbenzotriazoles and particularly that of 2-(1'-methyl)pentylbenzotriazole are outstanding; actually at the lowest concentration tested (10(-8) M and at 10(-5) M, at which concentration this compound shows the maximum activity, the biological responses correspond respectively to more than 50 and 80% of maximal activity of IAA.

Edible Grain↗
PubMed1977

Quantitative structure-activity relationship of chymotrypsin-ligand interactions.

Quantitative structure-activity relationships (QSAR) have been formulated for the interactions of a variety of ligands with chymotrypsin. The parameters Km, k2, k3, kcat, and Ki are found to be strongly dependent on molar refractivity as well as steric and electronic character of the substituents in structures of the type R2CH(COOR3)NHCOR1 where R may be H. A model for binding of D and L esters is presented which gives a consistent view of the binding step, acylation, and deacylation. The model suggests new avenue for exploration.

Acylation↗