0000000000162155
AUTHOR
F. J. García-march
Correlation of Pharmacological Properties of a Group of Hypolipaemic Drugs by Molecular Topology
Abstract This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F-Snedecor function values, Mallow's CP and Student's t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts these properties. Corresponding stability (cross validation) studies were made on the selected prediction models which confirmed their goodness of fit. The resul…
Calculation of chromatographic properties of barbiturates by molecular topology
A study has been made of the relationship between the RF values obtained by thin layer chromatography for a group of barbiturates and the connectivity indices proposed by Kier and Hall. By using multivariable regression we obtained the corresponding connectivity functions, which were selected on the basis of their respective statistics parameters. The regression analysis of the connectivity functions shows a correct prediction of the experimental elution sequence for this group of molecules on silicagel with two mobile phases of different polarity. The corresponding random and stability studies of the different prediction models selected were carried out, demonstrating good stability and nu…
New Analgesics Designed by Molecular Topology
Molecular topology has been applied to the design of new analgesic drugs, utilizing linear discriminant analysis and connectivity functions using different topological descriptors. Of a total of 26 compounds selected, 17 showed analgesic activity. The following stood out particularly, showing analgesic values greater than 75% regarding ASA (acetylsalicylic acid), the reference drug: 2-(1-propenyl)phenol, 2′4′ dimethylacetophenone, p-chlorobenzohydrazide, 1-(p-chlorophenyl) propanol and 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one. The usefulness of the design method has been demonstrated in the search of new chemical structures having analgesic effects, some of which could become “lead dru…
New Hypolipaemic Agents Designed by Molecular Topology: Pharmacological Studies of 2,6-Di-tert-butyl-4-methylpyridine and 2,6-Di-tert-butylpyridine
New compounds showing hypolipaemic activity have been designed using a computer-aided method based on molecular topology and QSAR analysis. Linear discriminant analysis and connectivity functions were used to design three potentially suitable drugs which were tested for hypolipaemic properties by the Triton WR-1339 test in rats. The pharmacological tests carried out on the newly designed compounds demonstrated the existence of notable activity in phase I for two of them. namely 2,6-Di-tert-butyl-4-methylpyridine (C.A.S. 38222-83-2) and 2,6-Di-tert-butylpyridine (C.A.S. 585-48-8), with respect to the level of total cholesterol. Both substances decrease the lipaemia to lower levels than clofi…
QSAR Analysis of Hypoglycemic Agents Using the Topological Indices
The molecular topology model and discriminant analysis have been applied to the prediction of some pharmacological properties of hypoglycemic drugs using multiple regression equations with their statistical parameters. Regression analysis showed that the molecular topology model predicts these properties. The corresponding stability (cross-validation) studies performed on the selected prediction models confirmed the goodness of the fits. The method used for hypoglycemic activity selection was a linear discriminant analysis (LDA). We make use of the pharmacological distribution diagrams (PDDs) as a visualizing technique for the identification and selection of new hypoglycemic agents, and we …
Discrimination and selection of new potential antibacterial compounds using simple topological descriptors.
Abstract The aim of the work was to discriminate between antibacterial and non-antibacterial drugs by topological methods and to select new potential antibacterial agents from among new structures. The method used for antibacterial activity selection was a linear discriminant analysis (LDA). It is possible to obtain a QSAR interpretation of the information contained in the discriminant function. We make use of the pharmacological distribution diagrams (PDDs) as a visualizing technique for the identification and selection of new antibacterial agents.
Artificial neural network applied to prediction of fluorquinolone antibacterial activity by topological methods.
A new topological method that makes it possible to predict the properties of molecules on the basis of their chemical structures is applied in the present study to quinolone antimicrobial agents. This method uses neural networks in which training algorithms are used as well as different concepts and methods of artificial intelligence with a suitable set of topological descriptors. This makes it possible to determine the minimal inhibitory concentration (MIC) of quinolones. Analysis of the results shows that the experimental and calculated values are highly similar. It is possible to obtain a QSAR interpretation of the information contained in the network after the training has been carried …
Calculation of chromatographic parameters by molecular topology: sulphamides
This investigation was undertaken to test the ability of the molecular connectivity model to predict RF values in thin-layer chromatography (TLC) for a group of sulphamides using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, F-Snedecor function values and Student's t-test as criteria of fit. Regression analyses showed that the molecular connectivity model predicts the values for this property in different silica gel stationary phases and different polar mobile phases. Corresponding stability and random studies were made on the selected prediction models which confirmed their goodness of fit. The results also demonstrated that differe…
Pharmacological studies of 1-(p-chlorophenyl)propanol and 2-(1-hydroxy-3-butenyl)phenol: Two new non-narcotic analgesics designed by molecular connectivity
Abstract Molecular topology has been applied to the design of new analgesic drugs. Linear discriminant analysis and connectivity functions were used to design two potentially suitable drugs which were synthesized and tested for analgesic properties by the acetic acid-induced abdominal constriction test in mice and the tail-flick test in rats. In mice, the compound 1-(p-chlorophenyl)propanol showed higher analgesic activity, both intraperitoneally and orally, than acetylsalicylic acid. 2-(1-Hydroxy-3-butenyl)phenol exhibited a lesser protective effect (70% of that shown by acetylsalicylic acid). In rats, acetylsalicylic acid gave the greatest protection against pain when administered intrape…
Prediction of chromatographic parameters for some anilines by molecular connectivity
The possible relation existing between RF values obtained by thin-layer chromatography for a group of anilines with connectivity indices proposed by Kier and Hall has been studied. Using multivariable regression the corresponding connectivity functions, selected for their respective correlation coefficients, standard deviations, Snedecor's F and Student's t were obtained. Regression analysis of the connectivity functions gives a correct prediction of the experimental elution sequence for this group of substances on silica gel stationary phases and various mobile phases of different polarity. The corresponding random and stability studies of the different prediction models selected were carr…