Electron-topological Method Research Articles

Study of the relationship between chemical structure and antimicrobial activity in a series of hydrazine-based coordination compounds.

The dependence of antimicrobial activity on the structure of compounds is studied in a series of compounds based on hydrazine coordinated with ions of Cu(II), Ni(II) and Pd(II). The study has been carried out by means of the original electron-topological method developed earlier. A molecular fragment has been found that is only characteristic of biologically active compounds. Its spatial and electron parameters have been used for the quantitative assessment of the activity in view. The results obtained can be used for the antimicrobial activity prediction in a series of compounds with similar structures.

Three-dimensional model of nonsteroidal estrogen receptor ligand binding/electron topological method.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models have been obtained using the electron topological method (ETM) for estrogen (estrone, CAS 53-16-7) receptor (ER) affinities. This method was used to identify regions of the enzyme and inhibitors where steric and electrostatic effects correlate strongly with biological activity. Thirty compounds belong to a series of diethylstilbestrol (CAS 56-53-1, DES) and indenestrol (CAS 24643-94-5) analogues whose affinities for ER have been, theoretically, investigated. After energy minimizations and molecular dynamics calculations were performed to find the ground state conformer for each molecule, quantum chemical properties of each molecule were defined and in ETM their matrices were compared with those of the reference molecule. It is shown that the molecular fragments responsible for this affinity possess fixed electronic and geometric characteristics associated with a distinct arrangement and steric accessibility of an oxygen atom and a group of carbon atoms. Several parameters were modified in order to analyze their influence onto the correlation between binding affinities. The highest correlation coefficient (R2 = 0.930, SE = 0.403) was obtained with the structure of the active fragment and the orientation of aliphatic and phenolic substituents.

4D-QSAR Study of p56IckProtein Tyrosine Kinase Inhibitory Activity of Flavonoid Derivatives Using MCET Method

A four dimensional quantitative structure activity relationship analysis was applied to a series of 50 flavonoid inhibitors of <TEX>$p56^{lck}$</TEX> protein tyrosine kinase by the molecular comparative electron topological method. It was found that the -log (IC50) values of the compounds were highly dependent on the topology, size and electrostatic character of the substituents at seven positions of the flavonoid scaffold in this study. Depending on the negative or positive charge of the groups correctly embedded in these substituents, three-dimensional bio-structure to increase or decrease -log (IC50) values in the training set of 39 compounds was predicted. The test set of 11 compounds was used to evaluate the predictivity of the model. To generate 4D-QSAR model, the defined function groups and pharmacophore used as topological descriptors in the calculation of activity were of sufficient statistical quality (<TEX>$R^2$</TEX> = 0.72 and <TEX>$Q^2$</TEX> = 0.69). Ligand docking approach by using Dock 6.0. These compounds include many flavonoid analogs, They were docked onto human families of p56lck PTKs retrieved from the Protein Data Bank, 1lkl.pdb.

Investigation of Structure-Activity Relationship Between Chemical Structure and CCR5 Anti HIV-1 Activity in a Class of 1-[N-(Methyl)-N- (Phenylsulfonyl)Amino]-2-(Phenyl)-4-[4-(Substituted)Piperidin-1-yl]Butane Derivatives: The Electronic-Topological Approach

The relationship between chemical structure and CCR5 anti HIV-1 activity was investigated in the series of 1-[N-(Methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-[4-(substituted) piperidin-1-yl]butanes derivatives including 114 molecules by using the Electron-Topological Method (ETM). In the frameworks of this approach, its input data were taken as the results of conformational and quantum-mechanical calculations. Conformational analysis and quantum-chemical calculations were carried out for each molecule. Then molecular fragments being specific for active molecules and non-active molecules were revealed by using ETM. The result of testing showed the high ability of ETM in predicting the activity and inactivity investigated series. In order to classify and to develop a model for those molecules, cluster and discriminant analyses are conducted. First, cluster analysis is implemented in order to classify similar molecules into the groups. Then, discriminant analysis is used to construct models including descriptors. By doing so, two obtained discriminant functions segregate those molecules into three different groups by using the descriptors called EHOMO, Dipole Moment and SEZPE.

The Investigation of Structure-Activity Relationships of Tacrine Analogues: Electronic-Topological Method

In this study we investigated the structure-activity relationships by using the Electron- Topological Method (ETM) for a class of AChE inhibitors related to tacrine (9-amino-1,2,3,4-tetrahydroacridine) and 11 H-Indeno-[1,2-b]-quinolin-10-ylamine that tetracyclic tacrine analogues, a drug currently in use for the treatment of the AD. Molecular fragments being specific for active and inactive compounds were revealed by using ETM. The result of testing showed the high ability of ETM in predicting the activity and inactivity in investigated series.

Electron-Topological Method of the Non-Nucleoside HIV-1 RT Inhibitors Study: Structure-Activity Relationships

Structure activity relationships for a series of TIBO (4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-j,k][1,4] benzodiazepin-2(1H)-one) derivatives, which significantly inhibit HIV-1 replication are analyzed by the Electron-Topological Method (ETM) and Artificial Neural Networks (ANNs). Activities of the TIBO series including 91 compounds are given as IC(50). Conformational analysis and quantum-chemical calculations are carried out for each TIBO derivatives, and then molecular fragments being specific for active compounds and non-active compounds are revealed by using ETM. In this study, we used optimized geometry data and electronic characteristics to form Electron-Topological Matrices of Contiguity (ETMCs) for all compounds in the series of TIBO derivatives. Effective charges on atoms are taken as diagonal elements, bond characteristics and optimized distances represent non-diagonal elements. To obtain the algorithmic base for the activity prediction, ANNs were used after the ETM (the so-called combined ETM-ANN method). As the result, 6 pharmacophores and anti-pharmacophores were chosen as the most important ones. The statistical coefficients calculated by the proposed algorithm were q(2)=0.82, for training set and q(2)= 0.72, for external test set respectively Thus, the found results showed that ETM-ANNs approach is a good convenient tool for QSAR studies.

Study of the binding affinity for corticosteroid-binding globulin (CBG) using the electron topological method (ETM) as three-dimensional quantitative structure–activity relationship (3D QSAR)

The Electron Topological Method, called ETM, is a descriptor for predicting the biological activities of molecules based on three-dimensional quantitative structure–activity relations (3D QSAR). ETM uses a modified electron topological state index to substitute for electronic properties and a topological distance for the relative distance in the molecule. It is shown that the molecular fragments responsible for this activity possess fixed electronic and geometric characteristics associated with a distinct arrangement and the steric accessibility of an oxygen atom and a group of carbon atoms. After that, it is essential to employ a linear regression analysis technique to derive a 3D QSAR model relating the biological activities to the ETM. The ETM is used to study the 3D QSAR of the corticosteroid-binding globulin (CBG) binding affinity to 31 steroids, and resulting models have a comparable to current 3D methods such as CoMFA. Though the ETM is a descriptor based on 3D topological information obtained by quantum chemical derived descriptors, give the best answer for both the similarity analysis and the statistical fitting.

Investigation of antiulcer activities of imidazo[1,2-alpha]pyridinyl-2-alkylaminobenzoxazoles and 5,6,7,8-tetahydroimidazo[1,2-alpha]pyridinyl-benzoxazoles with electron-topological (ET) method.

The study presents structure-activity considerations of a series of imidazo[1,2-alpha]pyridiny-2-alkylaminobenzoxazoles(I) and 5,6,7,8-tetahydroimidazo[1,2-alpha]pyridinylbenzoxazoles(II) investigated for anti-stress ulcer activity with the electron-topological method. A series of 39 compounds including 24 active and 15 weakly active was studied. It is shown that the fragment determined by the electron-topological method in an active molecule is responsible for anti-stress ulcer activity. Quantitative structure-activity relationships with electron topological approach of these compounds are discussed in terms of the statistical program STATGRAF-7.0.

Study of electronic and structural features of thiosemicarbazone and thiosemicarbazide derivatives demonstrating anti-HSV-1 activity

The structure–activity relationships (SAR) in a series of thiosemicarbazone and thiosemicarbazide derivatives (60 compounds) have been investigated by means of the Electron-Topological Method (ETM). All derivatives in the training set are potent inhibitors of herpes simplex virus type 1 (HSV-1) replication (C. Shipman, S.H. Smith, J.C. Drach, D.L. Klayman, Antiviral Research, 6 (1986) 197–222). On the basis of geometrical and electronic data calculated for each compound and arranged in a matrix form, two features of activity and three breaks of activity have been revealed. By means of the method of multivariable regression a quantitative model was built to express the activity dependence on some physicochemical and structural parameters.

Study of the electronic and structural features characteristic of 4,5-dihydro-1-phenyl-1H-2,4-benzodiazepines demonstrating antiarrhythmic activity

The relationships between the structure of the compounds and their antiarrhythmic activities have been investigated in a series of 4,5-dihydro-1-phenyl-1H-2,4-benzodiazepines (54 compounds) by means of the electron-topological method. As a result of the approach applied, two fragments characteristic of two kinds of activities demonstrated by the compounds have been found and studied. The system of prognostication developed on the base of the data obtained is being used for screening and search of new active antiarrhythmic agents.

Structure-odour relationships: results of an applied electron-topological approach.

Relationships between odour and chemical structure of compounds are studied by means of the electron-topological method developed for structure/activity research especially. A brief explanation is given for distinguished features of the method. Application examples are demonstrated for sandalwood, ambergris odour, garlic aroma and meat keynotes in food additives. The structural fragments affecting the odour appearance are revealed and discussed with respect to their electronic and topological peculiarities. The latter are formulated as rules for activity prediction of new compounds with special properties.

Study of the structure—activity relationship in a series of buspirone analogs by the electron-topological method

Study of the structure—activity relationship in a series of buspirone analogs by the electron-topological method

Structural characteristics of sulfanilamides with antimicrobial activity

Interest in the search for new sulfanilamide drugs has not abated: this interest is due both to the wide spectrum of their action and to the relatively inexpensive production of this drug [1, 2]. In our work the electron topological method (ETM) was used to study the structure-activity relationship (SAR) in a series of antimicrobial sulfanilamides (see Tables 1 3). The initial selection comprised 47 compounds, among which 30 were considered active and 17 inactive compounds. The presence of antimicrobial activity in vitro, log I/CR provided grounds for dividing the number of compounds into active and inactive ones. Compounds showing 4.3 < log 1 /Ca < 6.1 and log 1/CR < 4.0 were generally considered active and inactive, respectively [3]. All compounds have the common sulfanilamide framework with a wide variety of substituants attached to the sulfanilamide group. This is responsible for considerable variations in the activity parameter (,4) in the series under investigation. The electron topological method for the SAR study [4 6] developed by us was used for this series of compounds. Compound 25 was selected as a reference compound, since among active compounds its structure was the simplest. OH On ., ~ \\ / / C~N, .Ni'C 2 //x"-"S 3 II \\ H~ ~ ~ "N~C5 / C ~ I \S6 Ht3

Study of the structure-activity relationship in a number of antimicrobial sulfanilamine compounds by an electron-topological method

Study of the structure-activity relationship in a number of antimicrobial sulfanilamine compounds by an electron-topological method