QSAR MODELING OF ANTIBACTERIAL ACTIVITY OF SOME BENZIMIDAZOLE DERIVATIVES

A quantitative structure-activity relationship (QSAR) study has been carried out for a training set of 12 benzimidazole derivatives to correlate and predict the antibacterial activity of studied compounds against Gram-negative bacteria Pseudomonas aeruginosa. Multiple linear regression was used to select the descriptors and to generate the best prediction model that relates the structural features to inhibitory activity. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based on the following descriptors: parameter of lipophilicity (logP) and hydration energy (HE). Good agreement between experimental and predicted inhibitory values, obtained in the validation procedure, indicated the good quality of the generated QSAR model

Physico-chemical characterization and anti- microbial activity of copper(II) complexes with 2-amino and 2-methylbenzimidazole derivatives

Copper(II) chloride, in warm ethanolic solution, reacted with 2-amino and 2-methylbenzimidazole derivatives to give complexes of the formula CuL2Cl2·nH2O, where L=1-benzyl-2-aminobenzimidazole 1-(4-methylbenzyl)-2-aminobenzimidazole, 1-benzyl-2-methylbenzimidazole and 1-(4-methylbenzyl)-2-methylbenzimidazole( n=1 or 2). The complexes were characterized by elemental analysis of the metal, molar conductivity magnetic susceptibility measurements and IR spectra. The molar conductivities of copper(II)complexes in dimethyl formamide (DMF) corresponding to a 1:1 type of electrolyte indicate that in all the complexes one of the coordinated chloride ions has been replaced by DMF molecule. The room temperature effective magnetic moments and IR data of the complexes suggest that all Cu(II) complexes have a tetrahedral configuration, which is realized by participation of the pyridine nitrogen of two organic ligand molecules and two chloride anions. The antimicrobial activity of the ligands and their complexes against Pseudomonas aeruginosa, Bacillus sp. Staphylococcus aureus, Sarcina lutea and Saccharomyces cerevisiae was investigated. The effect of copper complexation on the ligand antimicrobial activity is discussed

Quantitative structure-activity relationship of some 1-benzylbenzimidazole derivatives as antifungal agents

In the present study, the antifungal activity of some 1-benzylbenzimidazole derivatives against yeast Saccharomyces cerevisiae was investigated. The tested benzimidazoles displayed in vitro antifungal activity and minimum inhibitory concentration (MIC) was determined for all the compounds. Quantitative structure-activity relationship (QSAR) has been used to study the relationships between the antifungal activity and lipophilicity parameter, logP, calculated by using CS Chem-Office Software version 7.0. The results are discussed on the basis of statistical data. The best QSAR model for prediction of antifungal activity of the investigated series of benzimidazoles was developed. High agreement between experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on antifungal activity of this class of compounds, which simplify design of new biologically active molecules

Synthesis, physico-chemical characterization and biological activity of 2-aminobenzimidazole complexes with different metal ions

Complexes of 2-aminobenzimidazole (L) with nitrates of cobalt(II) nickel(II), copper (II), zinc(II) and silver(I) were synthesized. The molar ratio metal:ligand in the reaction of the complex formation was 1:2. It should be noticed, that the reaction of all the metal salts yielded bis(ligand) complexes of the general formula M(L)2(NO3)2 × nH2O (M=Co, Ni Cu, Zn or Ag; n=0, 1, 2 or 6). The complexes were characterized by elemental analysis of the metal, molar conductivity, magnetic susceptibility measurements and IR spectra. Co(II), Ni(II) and Cu(II) complexes behave as non-electrolytes, whilst Zn(II) and Ag(I) are 1:1 electrolytes. Cu(II) complex has a square-planar stereochemistry, Ag(I) complex is linear, whilst the Co(II), Ni(II) and Zn(II) complexes have a tetrahedral configuration. In all the complexes ligand is coordinated by participation of the pyridine nitrogen of the benzimidazole ring. The antimicrobial activity of the ligand and its complexes against Pseudomonas aeruginosa, Bacillus sp. Staphylococcus aureus and Saccharomyces cerevisiae was investigated. The effect of metal on the ligand antimicrobial activity is discussed

Neural network modelling of antifungal activity of a series of oxazole derivatives based on in silico pharmacokinetic parameters

In the present paper, the antifungal activity of a series of benzoxazole and oxazolo[ 4,5-b]pyridine derivatives was evaluated against Candida albicans by using quantitative structure-activity relationships chemometric methodology with artificial neural network (ANN) regression approach. In vitro antifungal activity of the tested compounds was presented by minimum inhibitory concentration expressed as log(1/cMIC). In silico pharmacokinetic parameters related to absorption, distribution, metabolism and excretion (ADME) were calculated for all studied compounds by using PreADMET software. A feedforward back-propagation ANN with gradient descent learning algorithm was applied for modelling of the relationship between ADME descriptors (blood-brain barrier penetration, plasma protein binding, Madin-Darby cell permeability and Caco-2 cell permeability) and experimental log(1/cMIC) values. A 4-6-1 ANN was developed with the optimum momentum and learning rates of 0.3 and 0.05, respectively. An excellent correlation between experimental antifungal activity and values predicted by the ANN was obtained with a correlation coefficient of 0.9536. [Projekat Ministarstva nauke Republike Srbije, br. 172012 i br. 172014

LIPOPHILICITY AND ANTIFUNGAL ACTIVITY OF SOME 2-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES

In the present paper, the antifungal activity of some 2-methyl and 2-amino-benzimidazole derivatives was evaluated against yeast Saccharomyces cere¬visiae. The tested compounds displayed in vitro antifungal activity and mini¬mum inhibitory concentration (MIC) was determined for all compounds. The partition coefficients of the studied compounds were measured by the shake flask method (log P) and by theoretical calculation (Clog P). The log P values were compared and the relationships between the logP values and antifungal activities were investigated. The mathematical models have been developed as calibration models for predicting the antifungal activity of this class of com¬pounds. The quality of models was validated by the leave-one-out (LOO) technique as well as by the calculation of statistical parameters for the esta¬blished models. The results of the present study may be useful for the de¬signing of new more potent benzimidazole derivatives against yeast Sac-charo¬myces cerevisiae

Quantitative structure-activity relationships to predict antibacterial effect of some benzimidazole derivatives

The antibacterial activity of some substituted benzimidazole derivatives against Gram negative bacteria Escherichia coli was investigated. The tested compounds displayed in vitro inhibitory activity and their minimum inhibitory concentrations were determined. Quantitative structure-activity relationship has been used to study the relationships between the antibacterial activity and lipophilicity parameter, logP. Lipophilicity parameters were calculated for each molecule by using CS Chem-Office Software version 7.0. Multiple linear regression was used to correlate the logP values and antibacterial activity of benzimidazole derivatives. The results are discussed on the basis of statistical data. The most acceptable QSAR model for prediction of antibacterial activity of the investigated series of benzimidazoles was developed. High agreement between experimental and predicted inhibitory values was obtained. The results of this study indicate that the lipophilicity parameter has a significant effect on antibacterial activity of this class of compounds, thus simplifying design of new biologically active molecules

CORRELATIONS BETWEEN THE LIPOPHILI- CITY AND THE INHIBITORY ACTIVITY OF DIFFERENT SUBSTITUTED BENZIMIDAZOLES

2-Amino and 2-methylbenzimidazole derivatives were tested in vitro for their inhibitory activity against the bacteria Bacillus cereus. The minimum inhibitory concentration (MIC) was determined for all compounds. The lipophilicity descriptors were calculated by using CS Chem-Office Software, version 7.0. The stepwise regression method was used to derive the most significant model as a calibration model for predicting the antibacterial activity of this class of compounds. A complete regression analysis resorting to linear and quadratic relationships was made. Theoretical models were validated by leaving one out (LOO) technique, as well as by the calculation of statistical parameters for the established models. The best QSAR model for the prediction of an inhibitory activity of the investigated series of benzimidazoles was developed. A high agreement between the experimental and predicted inhibitory values was obtained. The results indicated that the antibacterial activity could be modeled using the lipophilicity descriptor. Key words: benzimidazole; antibacterial activity; quantitative structure-activity relationship; lipophilicity; in vitro studies; Bacillus cereus. The benzimidazole functional group plays important roles in numerous bioactive compounds. The literature indicated that the benzimidazole nucleus is an essential part of many clinically useful chemotherapeutic agents. Currently, benzimidazole derivatives are the subject of sustained interest due to the vast range of their potential activities. Biologically active benzimidazoles have been known for a long time and they can act as bacteriostats or bactericides In this context, the aim of the present work was to investigate the activity of different substituted benzimidazoles against Gram-positive bacteria Bacillus cereus and to study the quantitative effect of lipophilicity on an antibacterial activity. The central objective of the study was to select the most significant QSAR model which links the structure of these compounds with their inhibitory activity

Antibacterial and antifungal activity of zinc(II) complexes with some 2-methylbenzimidazole derivatives

Zinc(II) chloride reacts with 2-methylbenzimidazole derivatives to give complexes of the formula ZnL2Cl2-nH2O, where L=2-methylbenzimidazole l-benzyl-2-methylbenzimida-zole and l-(4-methylbenzyl)-2-methylbenzimidazole n=0, 0.5 or 1. All the ligands and their zinc(II) complexes were evaluated for their in vitro antimicrobial activity against Pseudomonas aeruginosa Bacillus sp., Staphylococcus aureus, Sarcina lutea and Candida pseudotropicalis. It was found that the majority of the investigated compounds displayed in vitro antimicrobial activity against very persistent microorganisms, except for the starting ligand, 2-methylbenzimidazole and its zinc(II) complex which were active only against gram-negative bacteria. None of the compounds was significantly effective against Candida pseudotropicalis, except for l-(4-methylbenzyl)-2-methylbenzimidazoleandits complex, which very slightly or slightly inhibited the yeast growth. The minimum inhibitory concentration (MIC) was determined for all the ligands and their complexes. The effect of ligand and complex structure on the antimicrobial activity was discussed

Correlation and principal component analysis in ceramic tiles characterization

The present study deals with the analysis of the characteristics of ceramic wall and floor tiles on the basis of their quality parameters: breaking force, flexural strenght, absorption and shrinking. Principal component analysis was applied in order to detect potential similarities and dissimilarities among the analyzed tile samples, as well as the firing regimes. Correlation analysis was applied in order to find correlations among the studied quality parameters of the tiles. The obtained results indicate particular differences between the samples on the basis of the firing regimes. However, the correlation analysis points out that there is no statistically significant correlation among the quality parameters of the studied samples of the wall and floor ceramic tiles.[Projekat Ministarstva nauke Republike Srbije, br. 172012 i br. III 45008