Molecular modeling and QSAR analysis of some 4,5-dichloroimidazolyl-1,4-DHP-based calcium channel blockers

Abstract

The effects of the structural features of some 4,5-dichloroimidazolyl-1,4-dihydropyridine on their calcium channel antagonist activity have been studied using molecular modeling and quantitative structure activity-relationship analysis. Both symmetrical and asymmetrical dihydropyridine derivatives were used. AM1 semi-empirical quantum chemical calculation was used to find the optimum 3-D geometry of the molecules. Four different sets of descriptors, including chemical, topological, quantum chemical and substituent constant, were then calculated for each molecule. For each set of descriptors, the best multilinear QSAR equations were obtained by the stepwise variable selection method using leave-one-out cross-validation as selection criterion. Separate QSAR models were first obtained for symmetrical and asymmetrical derivatives, after which a general model was proposed for the entire set of molecules. This model has root mean square error of 0.45 and reproduces more than 82% of the variances in the calcium channel antagonist activity data. The sum of the negative charges, the energy of the highest occupied molecular orbital, molecular volume and the least negative charge were identified as the most significant descriptors.

A Kinetic spectrophotometric method for determination of amlodipine and Nifedipine in pharmaceutical preparations

“…They are mainly used as antianginal, anthihypertensive and antiarrythmic agents [1][2][3]. AML and NIF, similar to the other DHP derivatives, are photosensitive and are converted to inactive and even toxic products when they are irradiated by ultraviolet or visible lights [4][5][6][7][8][9].…”

Exploring QSAR for Substituted 2‐Sulfonyl‐Phenyl‐Indol Derivatives as Potent and Selective COX‐2 Inhibitors Using Different Chemometrics Tools

“…Multiple linear regression (MLR), principal component regression (PCR) and partial least square (PLS) are the mostly commonly used modeling methods in QSAR, among which MLR yields models that are simpler and easier to interpret since the latter perform regression on principal components of latent variables, which are mathematical in nature and it is difficult to interpret them chemically (33). On the other hand, MLR analysis fails to give accurate results in the presence of collinear variables or when number of descriptors is large comparing with the number of molecules whereas by orthogonalization of the variables into low dimensional space, the factor analysis-based methods such as PCR and PLS can overcome the drawbacks encountered for MLR (34). Variable selection, as an inseparable part of the model development in QSAR studies, is used to select the most informative subset of descriptors representing significant effects on the biological activity of interest (35).…”

QSAR studies on the antiviral compounds of natural origin

“…Molecular descriptors can be collected form different sources such as substituent constants, physicochemical properties, quantum chemical calculations and the theoretical structural parameters derived from one or two dimensional molecular structures [31]. Theoretical descriptors such as constitutional descriptors and topological indices have found the major popularity in QSAR studies for many reasons such as a) their calculation are simple and fast, b) they do not need information about three-dimensional structure of molecules, c) they are exact number without uncertainty and d) they represent high correlation with many biological activities [31][32][33][34][35].…”