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QSAR Study on tadpole narcosis 总被引:1,自引:0,他引:1
Agrawal VK Chaturvedi S Abraham MH Khadikar PV 《Bioorganic & medicinal chemistry》2003,11(20):4523-4533
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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. 相似文献
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Khadikar PV Singh S Mandloi D Joshi S Bajaj AV 《Bioorganic & medicinal chemistry》2003,11(23):5045-5050
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. 相似文献
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The aqueous solubility (S(w)) of liquids and solids, expressed as log S(w) as well as their partition coefficients in different solvent systems viz. P(oct) (partition coefficient in octanol-water), P(16) (partition coefficient in water-hexadecane), P(alk) (partition coefficient in water-alkane), and P(cyc) (partition coefficient in water-cyclohexane), and aqueous solubility (S(w)) have been estimated using the PI (Padmakar-Ivan) index and the results compared with those obtained using the widely used Wiener index (W). Regression analysis of the data using n-alkanes show that the PI index gives better results than the W index. 相似文献
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Thakur A Thakur M Khadikar PV Supuran CT Sudele P 《Bioorganic & medicinal chemistry》2004,12(4):789-793
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. 相似文献
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We previously reported a classical quantitative structure-activity relationship (QSAR) equation for permeability coefficients (P(app-pampa)) by parallel artificial membrane permeation assay (PAMPA) of structurally diverse compounds with simple physicochemical parameters, hydrophobicity at a particular pH (logP(oct) and |pK(a)-pH|), hydrogen-accepting ability (SA(HA)), and hydrogen-donating ability (SA(HD)); however, desipramine, imipramine, and testosterone, which have high logP(oct) values, were excluded from the derived QSAR equation because their measured P(app-pampa) values were lower than calculated. In this study, for further investigation of PAMPA permeability of hydrophobic compounds, we experimentally measured the P(app-pampa) of more compounds with high hydrophobicity, including several pesticides, and compared the measured P(app-pampa) values with those calculated from the QSAR equation. As a result, compounds having a calculated logP(app-pampa)>-4.5 showed lower measured logP(app-pampa) than calculated because of the barrier of the unstirred water layer and the membrane retention of hydrophobic compounds. The bilinear QSAR model explained the PAMPA permeability of the whole dataset of compounds, whether hydrophilic or hydrophobic, with the same parameters as the equation in the previous study. In addition, PAMPA permeability coefficients correlated well with Caco-2 cell permeability coefficients. Since Caco-2 cell permeability is effective for the evaluation of human oral absorption of compounds, the proposed bilinear model for PAMPA permeability could be useful for not only effective screening for several drug candidates but also the risk assessment of chemicals and agrochemicals absorbed by humans. 相似文献
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Seelam J Satuluri VS Gupta SP Anwer Z 《Indian journal of biochemistry & biophysics》2011,48(3):158-163
Among the cardiotonics (agents against congestive heart failure), the most important group is of the digitalis cardiac glycosides, but since these compounds suffer from a low therapeutic index, attention has been paid to investigating safer cardiotonic agents through the inhibition of Na+,K(+)-ATPase, the mechanism by which the digitalis cardiac glycosides elicit their action. Recently, a series of perhydroindenes were studied for their Na+,K(+)-ATPase inhibition activity. We report here a QSAR study on them to investigate the physicochemical and structural properties of the molecules that govern their activity in order to rationalize the structural modification to have more potent drugs. A multiple regression analysis reveals a significant correlation between the Na+,K(+)-ATPase inhibition activity of the compounds and Kier's first order valence molecular connectivity index of their R5-substituents and some indicator parameters, suggesting that the R5-substituents of the compounds containing atoms with low valence and high saturation and the R1-substituents having =N-O- moiety will be conducive to the activity. 相似文献
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Exploring QSAR of melatonin receptor ligand benzofuran derivatives using E-state index 总被引:2,自引:0,他引:2
Considering the recent challenge to the medicinal chemists for the development of selective melatonin receptor ligands, an attempt has been made to explore physicochemical requirements of benzofuran derivatives for binding with human MT1 and MT2 receptor subtypes and also to explore selectivity requirements. In this study, E-states of different common atoms of the molecules (calculated according to Kier and Hall) and physicochemical parameters (partition coefficient and molar refractivity) were used as independent variables along with suitable dummy parameters. The best equation describing MT1 binding affinity [n = 34, Q2 = 0.670, Ra2 = 0.790, R2 = 0.822, R = 0.907, s = 0.609, F = 25.8 (df 5, 28)] suggests that the binding affinity decreases as the value of n (number of CH2 spacer beside R2) increases while it increases with rise in electrotopological state values of different atoms of the benzofuran ring. Again, presence of methoxy group at R1 and hydrogen, unsubstituted phenyl or fluoro-substituted phenyl group at R2 is conducive to the MT1 binding affinity. The binding affinity decreases if furyl substitution at R3 position is present. The best equation describing MT2 binding affinity [n = 34, Q2 = 0.602, Ra2 = 0.755, R2 = 0.792, R = 0.890, s = 0.584, F = 213 (df 5, 28)] shows that the MT2 binding affinity depends on the similar factors as described for MT1 binding affinity; however, the contributions of the factors for the two affinities are different to some extent as evidenced from the regression coefficients. Among the selectivity relations, the best equation [n = 33, Q2 = 0.496 Ra2 = 0.681, R2 = 0.721, R = 0.849, s = 0.458, F = 18.1(df 4, 28)] suggests that MT2 binding increases with increase in value of n, presence of methoxy group at R1, and E-state values of different atoms of the benzofuran ring, while it decreases in presence of furyl group at R3 position. 相似文献
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Katritzky AR Dobchev DA Tulp I Karelson M Carlson DA 《Bioorganic & medicinal chemistry letters》2006,16(8):2306-2311
Protection times provided by 31 synthetic repellents against Aedes aegypti mosquitoes were correlated with the chemical structures of these repellents using Codessa Pro software. Two statistically significant quantitative models with R2 values of ca. 0.80 are presented and discussed. 相似文献
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Lysosomal beta-mannosidase (EC 3.2.11.25) has a functional size of 120-150 kDa, but the enzyme purified from guinea pig liver (GPL) reportedly gave a single band corresponding to a molecular mass of 110 kDa. In order to investigate the subunit structure and tissue-specific expression of beta-mannosidase, we prepared a polyclonal antibody against GPL beta-mannosidase in rabbits which immunoprecipitated beta-mannosidase activity, free from other lysosomal hydrolase activity. Following storage at -20 degrees C and SDS polyacrylamide gel electrophoresis in the presence of 2-mercaptoethanol, a sample of purified GPL beta-mannosidase gave a major Coomassie blue staining band at 97 kDa. This was confirmed by Western blot analysis, which also revealed a faster moving 37 kDa protein. In contrast, Western blot analysis of fresh GPL homogenate prepared in the presence of proteinase inhibitors showed a major band at 150 kDa. Upon freezing and thawing, we observed immunoreactive bands at 120 and 20 kDa and finally, immunoreactive bands at 97, 37 and 20 kDa. The formation of the 97, 37 and 20 kDa forms from the 150 kDa species was accelerated by an n-butanol/ether extraction of the associated lipids, suggesting some tight hydrophobic association of these subunits. In contrast to liver, both fresh and freeze-thawed preparations of guinea pig kidney (GPK) yielded only the 97, 37 and 20 kDa subunit forms confirming that these are the major beta-mannosidase subunits. Endo-F treatment converted both the liver and kidney 97 kDa into a 91 kDa form and the 37 kDa form into a 35 kDa form, whereas the 20 kDa form was unaffected. Total beta-mannosidase activity, as measured with the synthetic substrate 4MU-beta-mannoside was unaffected by dissociation of the 150 form into the 97, 37 and 20 kDa subunits, suggesting that these are the functional forms of the enzyme rather than proteolytic degradation products. 相似文献
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Sumbul Firdaus Anupam Dhasmana Vandana Srivastava Tasneem Bano Afreen Fatima Qazi Mohammad Sajid Jamal Roshan Jahan Gulshan Wadhwad Mohtashim Lohani 《Bioinformation》2015,11(3):122-126
Fullerenes have attracted considerable attention due to their unique chemical structure and potential applications which has
opened wide venues for possible human exposure to various fullerene types. Therefore, in depth knowledge of how fullerene may
interfere with various cellular processes becomes quite imperative. The present study was designed to investigate how the
presence of fullerene affect the binding of DNA with different enzymes involved in replication process. Different fullerenes were
first docked with DNA and then binding scores of different enzymes was analyzed with fullerene docked DNA. C30, C40 & C50
once docked with DNA, reduced the binding score of primase, whereas no significant change in the binding score was observed
with the helicase, ssb protein, dna pol δ, dna pol ε, ligase, DNA clamp, and topoisomerases. On the contrast, the binding score of
RPA14 decreases in fluctuating manner while interacting with increasing molecular weight of fullerene bound single-stranded
DNA complex. The study revealed the affect of fullerene family interacting with DNA on the binding pattern of enzymes involved
in replication process. Study suggests that the presence of most of fullerenes may not affect the activity of these enzymes necessary
for replication process whereas C30, C40 & C50 may disrupt the activity of primase, (strating point for DNA polymerase) its
docking score decreases from 13820 to 10702. 相似文献
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区域生态系统健康状况对区域可持续发展具有重要意义。基于"系统和谐"理念,构建区域生态系统健康评价体系,对毛集生态试验区生态系统及其4个子系统健康水平和演进趋势进行量化分析。结果表明:5年尺度上社会系统得分受人口健康水平及民众幸福感知强度制约而增幅不大;经济系统得分提高迅速,增幅达到149.5%,但负外部效应明显;自然系统健康水平先降低再增加,主要受湖泊生物多样性下降影响;风险系统得分先降低再增加,自然-经济-社会耦合系统发展失衡是导致风险水平激增的主要原因。区域生态系统健康各年评价结果均为亚健康隶属,正向隶属先增大后减小,环境负荷增大是造成区域生态系统弹性减弱,敏感性增强,发展活力降低的主要原因。 相似文献
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