Chem-bioinformatics: QSTR studies on TIBO derivatives.

In the present study, effort has been made to develop a mathematical model for the set of 19 (tetrahydromidazo [4,5,1-jk][1,4] benzodizepin-2(1H)-one) (TIBO) derivatives. The biological activity modeled in the present investigation is cytotoxic concentration (log 1/C). To investigate the cytotoxic behavior of TIBO derivatives, classical and nonconventional physicochemical properties are tested separately. Out of the two categories, the classical physicochemical properties play a dominating role in the modeling of cytotoxicity. On the basis of the results obtained and with the help of molecular modeling parameters, we discovered that the molecular property is most responsible for the cytotoxicity of TIBO derivatives.

SAR and QSAR studies: modelling of new DAPY derivatives.

This work describes QSAR and SAR studies on the inhibition of reverse transcriptase by 31 novel DAPY (diarylpyrimidine) derivatives using both topological and physicochemical properties and molecular modelling parameters along with indicator parameters. The application of a multiple linear regression analysis indicated that a combination of topological and physicochemical descriptors and the indicator parameters yielded a statistically significant model for the prediction of the activity, log 1/C (50% of effective concentration of DAPY derivatives for RTs). The modelling of some new potential DAPY compounds and their maximum active comformers for the inhibition of reverse transcriptase are made by quantum molecular modelling.

QSAR and SAR studies on the reduction of some aromatic nitro compounds by xanthine oxidase.

This work describes QSAR and SAR studies on the reduction of 27 aromatic nitro compounds by xanthine oxidase using both distance-based topological indices and quantum molecular descriptors along with indicator parameters. The application of a multiple linear regression analysis indicated that a combination of distance-based topological indices with the ad hoc molecular descriptors and the indicator parameters yielded a statistically significant model for the activity, log K (the reduction of aromatic nitro compounds by xanthine oxidase). The final selection of a potential aromatic nitro compound for the reduction by xanthine oxidase is made by quantum molecular modeling. We have found that, among the various parameters, the quantum Mulliken charge parameters on the fourth atom or para position relative to the nitro group correlated best with the activity.

Study on supramolecular complexing ability vis-à-vis estimation of pKa of substituted sulfonamides: dominating role of Balaban index (J).

The supramolecular complexing ability vis-à-vis pKa estimation of a large series of 43 sulfonamides was made using a series of molecular descriptors including topological indices. The set of topological indices chosen also contains Balaban (J) and a variety of Balaban type indices: J, Jz, Jm, Jv, Jc, and Jp. The results have shown that the most discriminating Balaban index (J) in multi-parametric regression analysis combined with indicator parameters yields excellent models and also establishes the superiority of the J index over other Balaban type indices. The statistics is improved when one of the indicator parameters is replaced by molar volume (MV). The results are discussed critically using a variety of statistics.

QSAR study on pK(a) vis-à-vis physiological activity of sulfonamides: a dominating role of surface tension (inverse steric parameter).

The paper describes the dominating role of surface tension (ST) on the modeling, monitoring, and estimating pK(a) for a large series of 43 substituted sulfonamides. Because of the direct correlation of ST with parachor (Pc) vis-a-vis molecular volume (MV), ST is considered as a steric parameter. Single as well as multi-parametric regressions have indicated that ST has a dominating role in QSAR of the set of sulfonamides used and that excellent results are obtained in multi-parametric regression analysis. The results are discussed critically on the basis of statistical parameters.

QSAR study of flavonoid derivatives as p56lck tyrosinkinase inhibitors.

QSAR studies on 104 flavonoid derivatives as p56lck protein tyrosine kinase inhibitors were performed using hydration energy and logP as predictor parameters. The results obtained demonstrate in detail, which specify that hydration energy and hydrophobic parameters of the compounds play a significant role in developing QSAR models. The significance of presence and absence of substituents on particular position is successfully explored with the help of indicator parameters. The results are critically discussed on the basis of multiple linear regression parameters.

Topological modeling of benzodiazepine receptor binding.

The present study reports the QSAR modeling of benzodiazepine receptor binding affinity (pIC(50)) for a large set of 70 benzodiazepine receptor ligands. The step-wise regression analysis indicated that out of the large pool of molecular descriptors used only hydration energy (He), hydrophobic parameter (pi(3,5)), steric parameter (E(s)(2,6)) are useful for giving statistically significant models. The results are discussed critically using multivariate regression analysis and cross-validation method.

QSAR study on phenolic activity: need of positive hydrophobic term (log P) in QSAR.

The phenolic activity (log 1/C) of a large series of phenols against L1210 leukaemia cells was modelled using physicochemical parameters other than conventional electronic and steric parameters. Attempts have also been made to examine need or otherwise of the hydrophobic parameter, log P, in such studies. The results have shown that contribution of log P in modelling log 1/C is favourable.

QSAR studies on psychotomimetic phenylalkylamines.

Quantitative Structure-Activity Relationship (QSAR) studies on a series of psychotomimetic phenylalkylamines have been made using a combination of Minimum Topological Difference (MTD) method and topological methodology. The topological indices used being a pool of distance-based topological indices. The regression analyses have shown that excellent results are obtained in multiparametric model containing MTD parameters, topological indices in that quantum chemical parameters has to be introduced. The predictive power of the proposed model is discussed on the basis of cross-validation parameters.

QSAR study on benzenesulphonamide carbonic anhydrase inhibitors: topological approach using Balaban index.

QSAR study on benzenesulphonamide carbonic anhydrase inhibitors has been made using the most discriminatory Balaban index (J). The regression analysis has shown that even in monoparametric regression this index gave excellent results. Furthermore, using the combination of the Balaban Index (J) with the first-order Randic connectivity index ((1)chi) and indicator parameters, tremendous improvement in the statistics has been observed. The results are critically discussed on the basis of regression data and cross-validation parameters.