QSAR study on (13)C NMR chemical shifts on carbinol carbon atoms

QSAR calculations of (13)C NMR chemical shifts (ppm, TMS=0) on carbinol carbon atoms have been attempted using a large set of distance based topological indices: Wiener (W)-, Szeged (Sz)-, PI (Padmakar-Ivan) and Connectivity ((m)chi, (m)chi(v)) indices. The regression analysis has shown that excellent results are obtained in multiparametric regression. The predictive power of the proposed models are discussed using cross-validated parameters.     

Carbonic anhydrase inhibitors: the first QSAR study on inhibition of tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides

QSAR study on the tumor-associated transmembrane carbonic anhydrase IX (CA IX) isoenzyme has been made using a large pool of distance-based topological indices : W, Sz, PI (0)chi, (1)chi, (2)chi,(0)chi(v), (1)chi(v), (2)chi(v). A combined set of 32 aromatic and heterocyclic compounds, including the six clinically used derivatives: acetazolamide, methazolamide, ethoxyzolamide, dichlorophenamide, dorzolamide, and brinzolamide are used for this purpose. The results have shown that the inhibition of the tumor-associated isoenzyme IX with aromatic and heterocyclic sulfonamides can be modeled excellently in multiparametric regression after introduction of indicator parameters. The predictive power of the models is discussed using probable error of correlation (PE), variance-inflation factor (VIF), and cross-validation parameters: PRESS, SSY, r(2) (cv) (S) PRESS, and PSE. This is the first report on QSAR study on inhibition of tumor-associated isoenzyme IX.     

Topological estimation of electronic absorption bands of arene absorption spectra as a tool for modeling their toxicity and environmental pollution

A novel application of distance-based topological indices : Wiener (W)-, Szeged (Sz)-, Padmakar-Ivan (PI)-, and Sadhana (Sd)-indices in modeling electronic absorption bands of arene absorption spectra has been described. It is demonstrated that all these indices correlate linearly with the logarithm of beta and para electronic absorption bands in several series of arene systems. The results have shown that our methodology is best suited for the estimation--lnlambda(beta), while comparatively less significant results are obtained in case of the estimation of lnlambda(p). The statistical analysis of the data have shown that PI index gives better results for modeling lnlambda(beta); while Sz index proved better for modeling lnlambda(p). The results are critically discussed on the basis of regression parameters and quality of correlation. Such a study will be useful as a tool for modeling toxicity of arene system as well as their environmental pollution.     

Quantitative structure-activity relationship studies on 5-phenyl-3-ureido-1,5-benzodiazepine as cholecystokinin-A receptor antagonists

Quantitative structure-activity relationship (QSAR) studies on a series of 5-phenyl-3-ureido-1,5-benzodiazepine-2,4-diones has been carried out using a pool of distance-based topological indices. Step-wise regression analysis indicated that penta-parametric regression expression containing Sz, B, Ip1, Ip2 and Ip3 is the most potent and selective for CCK-A affinity. The predictive potential of the model is discussed on the basis of cross-validation parameters as well as by estimating root mean square (RMSR) of the residuals.     

QSAR study on toxicity to aqueous organisms using the PI index

We have attempted to develop quantitative structure-toxicity relationships (QSTRs) to predict hydrophobicity (logP) as well as toxicity (pEC50 microm) of benzene derivatives using recently introduced Padmakar-Ivan (PI) index. The results have shown that both logP as well as pEC50 of benzene derivatives can be modelled excellently in multiparametric models in that the PI index and some indicator parameters are involved. The predictive ability of the models is discussed on the basis of the cross-validation method. The superiority of the PI index over several other topological indices is critically examined.     

QSAR study on bioconcentration factor (BCF) of polyhalogented biphenyls using the PI index

Attempt has been made to estimate the accuracy, predictive power, and domain of application of the PI (Padmakar-Ivan) index for modeling bioconcentration factor (BCF) of polyhalogenated biphenyls. Relative potential of PI index is investigated by comparing the results obtained using this index with those obtained from Wiener (W) and Szeged (Sz) indices. In addition, attempt has also been made to model hydrophobicity/lipophilicity (logP) of the polyhalogenated biphenyls using these indices. It was observed that these distance-based topological indices gave better results for modeling log BCF than logP.     

QSAR studies on the activation of the human carbonic anhydrase cytosolic isoforms I and II and secretory isozyme VI with amino acids and amines

The first QSAR study on the activation of the human secretory isoform of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), CA VI, with a series of amines and amino acids is reported. A large set of topological indices have been used to obtain several tri-/tetra-parametric models. We compared the CA VI activating QSAR models with those calculated for activation of the cytosolic human isozymes hCA I and hCA II. In addition, the effect of D- and L-amino acids as activators of hCA I, hCA II and of hCA VI as compared to those of structurally related biogenic amines was investigated for obtaining statistically significant and predictive QSAR equations. The obtained models are discussed using a variety of statistical parameters. The best models were obtained for hCA II activation, followed by hCA I, whereas the QSAR models for the activation of hCA VI were statistically weaker.     

QSAR studies on carbonic anhydrase inhibitors: a case of ureido and thioureido derivatives of aromatic/heterocyclic sulfonamides

QSAR studies on modelling of biological activity (hCAI) for a series of ureido and thioureido derivatives of aromatic/heterocyclic sulfonamides have been made using a pool of topological indices. Regression analysis of the data showed that excellent results were obtained in multiparametric correlations upon introduction of indicator parameters. The predictive abilities of the models are discussed using cross-validation parameters.     

QSAR study on the affinity of some arylpiperazines towards the 5-HT1A/alpha1-adrenergic receptor using the E-state index

QSAR models represent the relationship of biological activity with either physicochemical parameters or structural indices. QSAR study was performed on some arylpiperazines as 5-HT(1A)/alpha(1)-adrenergic receptor antagonists using E-state indices to identify the pharmacophoric requirements. It was found that some of the atoms played important roles to both activities and some played important role in selectivity of compound to the 5-HT(1A) antagonistic activity. The presence of COONHPr group at the ortho-position of the phenyl ring might be disadvantageous and Br at meta-position might be conducive to the activity. COOPr at the ortho-position might be disfavored the adrenergic alpha(1)-antagonistic activity, thus increase the selectivity.