Rec A-independent homologous recombination induced by a putative fold-back tetraplex DNA.

We have recently reported that a GC-rich palindromic repeat sequence presumably adopts a stable fold-back tetraplex DNA structure under supercoiling. To establish the biological significance of this structure, we inserted this sequence between two direct repeat sequences, separated by 200 bp, in a plasmid. We then investigated the effect of this sequence on homologous recombination events.

A palindromic repeat sequence adopts a stable fold back structure under supercoiling.

A synthetic deoxyoligonucleotide containing five palindromic repeats of GGATCC self assembles to form a parallel four-stranded structure held together by G-tetrads that shows slower mobility than duplex DNA. This structure is hypersensitive to S1 nuclease and resistant to DMS modification. The same oligonucleotide when cloned in a plasmid forms a different structure under supercoiling that persists stably even in the cleaved out insert.

QSTR with extended topochemical atom (ETA) indices. VI. Acute toxicity of benzene derivatives to tadpoles (Rana japonica).

structure-toxicity relationship (QSTR) studies have proved to be a valuable approach in research on the toxicity of organic chemicals for ranking chemical substances with respect to their potential hazardous effects on living systems. With this background, we have modeled here the acute lethal toxicity of 51 benzene derivatives with recently introduced extended topochemical atom (ETA) indices [Roy and Ghosh, Internet Electron J Mol Des 2:599-620 (2003)]. We also compared the ETA relations with non-ETA models derived from different topological indices (Wiener W, Balaban J, flexibility index, Hosoya Z, Zagreb, molecular connectivity indices, E-state indices and kappa shape indices) and physicochemical parameters (AlogP98, MolRef,H_bond_donor and H_bond_acceptor).

QSAR by LFER model of HIV protease inhibitor mannitol derivatives using FA-MLR, PCRA, and PLS techniques.

The present quantitative structure-activity relationship (QSAR) study attempts to explore the structural and physicochemical requirements of mannitol derivatives for HIV protease inhibitory activity using linear free energy related model of Hansch. QSAR models have been developed using electronic (Hammett sigma), hydrophobicity (pi), and steric (molar refractivity and STERIMOL L, B1, and B5) parameters of phenyl ring substituents of the compounds along with appropriate dummy variables. Whole molecular descriptors like partition coefficient (logP(calcd)) and molar refractivity (MR) were also tried as additional descriptors.

QSAR analyses of 3-(4-benzylpiperidin-1-yl)-N-phenylpropylamine derivatives as potent CCR5 antagonists.

CCR5 receptor binding affinity of a series of 3-(4-benzylpiperidin-1-yl)propylamine congeners was subjected to QSAR study using the linear free energy related (LFER) model of Hansch. Appropriate indicator variables encoding different group contributions and different physicochemical variables such as hydrophobicity (pi), electronic (Hammett sigma), and steric (molar refractivity, STERIMOL values) parameters of phenyl ring substituents of the compounds were used as predictor variables. The Hansch analysis explores the importance of the lipophilicity and electron-donating substituents for the binding affinity.

Evaluation of ascorbic acid as suppressor of cyclophosphamide induced lipid peroxidation using common laboratory markers.

The present study deals with exploration of lipid peroxidation induction capacity of cyclophosphamide, an anticancer drug, and in vitro evaluation of ascorbic acid as a suppressor of cyclophosphamide induced lipid peroxidation. Goat liver homogenate has been used as the lipid source. This evaluation was done by measuring the malondialdehyde, 4-hydroxy-2-nonenal, reduced glutathione and nitric oxide content of the tissue as markers of lipid peroxidation.

A study on ceftriaxone-induced lipid peroxidation using 4-hydroxy-2-nonenal as model marker.

4-Hydroxy-2-nonenal, an indicator of lipid peroxidation process. was used as model marker to explore ceftriaxone-induced lipid peroxidation in goat liver homogenate. Ceftriaxone was found to induce lipid peroxidation significantly.

QSAR of adenosine A3 receptor antagonist 1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives using chemometric tools.

Considering the potential of selective adenosine A3 receptor subtype ligands in the development of prospective therapeutic agents, an attempt has been made to explore physicochemical requirements of 1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives for A3 receptor binding. In this study, lipophilicity (logP), physicochemical substituent constants (pi, MR, sigma p) of phenyl ring substituents, and Wang-Ford charges of common atoms of the quinoxaline nucleus (calculated from molecular electrostatic potential surface of energy-minimized geometry using AM1 technique) were used as independent variables along with suitable dummy parameters. The best multiple linear regression (MLR) equation obtained from factor analysis (FA-MLR) as the preprocessing step could explain and predict 72.

Exploring 3D-QSAR of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists+.

Binding affinity data [Bioorg Med Chem (2004) 12:613-623] of thiazole and thiadiazole derivatives (n = 30) for the human adenosine A3 receptor subtype have been subjected to 3D-QSAR (Quantitative structure-activity relationships) analyses by molecular shape analysis (MSA) and molecular field analysis (MFA) techniques using Cerius2 Version 4.8. In the case of the MSA, the major steps were (1) generation of conformers and energy minimization; (2) hypothesizing an active conformer (global minimum of the most active compound); (3) selecting a candidate shape-reference compound (based on the active conformation); (4) performing pairwise molecular superimposition using the maximum common subgroup (MCSG) method; (5) measuring molecular shape commonality using MSA descriptors; (6) determining other molecular features by calculating spatial, electronic and conformational parameters; (7) selection of conformers; (8) generation of QSAR equations by genetic function algorithm (GFA) or stepwise regression.

Exploring selectivity requirements for COX-2 versus COX-1 binding of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines using topological and physico-chemical parameters.

Considering the current need for development of selective cyclooxygenase-2 (COX-2) inhibitors, an attempt has been made to explore physico-chemical requirements of 2-(5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridines for binding with COX-1 and COX-2 enzyme subtypes and also to explore the selectivity requirements. In this study, E-states of different common atoms of the molecules (calculated according to Kier & Hall), first order valence connectivity and physicochemical parameters (hydrophobicity pi, Hammett sigma and molar refractivity MR of different ring substituents) were used as independent variables along with suitable dummy parameters in the stepwise regression method. The best equation describing COX-1 binding affinity [n = 25, Q2 = 0.

QSAR by LFER model of cytotoxicity data of anti-HIV 5-phenyl-1-phenylamino-1H-imidazole derivatives using principal component factor analysis and genetic function approximation.

Cytotoxicity data of anti-HIV 5-phenyl-1-phenylamino-1H-imidazole derivatives were subjected to quantitative structure-activity relationship (QSAR) study using linear free energy related (LFER) model of Hansch using electronic (Hammett sigma), hydrophobicity (pi) and steric (molar refractivity and STERIMOL L, B1, B2, B3 and B4) parameters of phenyl ring substituents of the compounds, along with appropriate indicator variables. Principal component factor analysis (FA) was used as the data-preprocessing step to identify the important predictor variables contributing to the response variable and to avoid collinearities among them. The generated multiple linear regression (MLR) equations were statistically validated using leave-one-out technique.

QSAR of estrogen receptor modulators: exploring selectivity requirements for ER(alpha) versus ER(beta) binding of tetrahydroisoquinoline derivatives using E-state and physicochemical parameters.

Considering importance of developing selective estrogen receptor modulators (SERMs), the present paper explores selectivity requirements of tetrahydroisoquinoline derivatives for binding with ER(alpha) versus ER(beta) receptors using E-state index and physicochemical parameters. The best model [n=21, Q(2)=0.512, R(a)(2)=0.

QSPR modeling of the water solubility of diverse functional aliphatic compounds by optimization of correlation weights of local graph invariants.

The optimization of correlation weights scheme was used to model the water solubility (ln S) of diverse functional aliphatic compounds (n = 193). The optimized descriptor formulated based on the data of a training set (n = 96) generated statistically acceptable relations for the training set (r2 = 0.987), test set (n = 97; r2 = 0.

QSTR with extended topochemical atom indices. Part 5: Modeling of the acute toxicity of phenylsulfonyl carboxylates to Vibrio fischeri using genetic function approximation.

In continuation of our recent efforts to model the acute toxicity of 56 phenylsulfonyl carboxylates to Vibrio fischeri using principal component factor analysis, the present paper deals with modeling of the same data set with extended topochemical atom (ETA) indices using genetic function approximation (GFA) as the statistical tool. The statistical quality of the best model using ETA descriptors is as follows: n=56, Q2=0.771, Ra2=0.

Exploring QSAR of thiazole and thiadiazole derivatives as potent and selective human adenosine A3 receptor antagonists using FA and GFA techniques.

Binding affinity data of thiazole and thiadiazole derivatives (n=30) for human adenosine A3 receptor subtype have been subjected to Quantitative Structure-Activity Relationship (QSAR) analysis using quantum chemical and hydrophobicity parameters. Wang-Ford charges of the common atoms of the compounds [calculated from molecular electrostatic potential surface of energy minimized geometry using Austin Model 1 (AM1) technique] were used as independent variables apart from partition coefficient (logP) and suitable dummy parameters. The variables for the multiple regression analyses were selected based on principal component factor analysis (FA), and generated equations were statistically validated using leave-one-out technique.

QSAR modeling of anti-HIV activities of alkenyldiarylmethanes using topological and physicochemical descriptors.

Three series of anti-HIV data (reverse transcriptase inhibitory activity, cytopathicity data, and cytotoxicity data) of alkenyldiarylmethanes were modeled with physicochemical, topological and structural descriptors by multiple regression analysis using principal component factor analysis as the data pre-processing step. Molar refractivity was found to be a significant contributor in modeling all three data sets. Apart from this, partition coefficient, E-state index, valence connectivity and indicator parameters were important in modeling different activity series.

Exploring QSAR with E-state index: selectivity requirements for COX-2 versus COX-1 binding of terphenyl methyl sulfones and sulfonamides.

An attempt has been made to explore selectivity requirements for cyclooxygenase-2 (COX-2) versus cyclooxygenase-1 (COX-1) binding of terphenyl methyl sulfones and sulfonamides using electrotopological state (E-state) index and suitable indicator parameters. Multiple linear regression analyses produced statistically acceptable equations: the best relation based on 'all-possible-subsets regression' for COX-1 binding (n=18) showed predicted variance and explained variance of 0.675 and 0.

QSAR of adenosine receptor antagonists. Part 3: Exploring physicochemical requirements for selective binding of 1,2,4-triazolo[5,1-i]purine derivatives with human adenosine A3 receptor subtype.

Considering potential of selective adenosine A3 receptor antagonists in the development of prospective therapeutic agents, an attempt has been made to explore selectivity requirements of 1,2,4-triazolo[5,1-i]purine derivatives for binding with cloned human adenosine A3 receptor subtype. In this study, partition coefficient (logP) values of the molecules (calculated by Crippen's fragmentation method) and Wang-Ford charges of the common atoms of the triazolopurine nucleus (calculated from molecular electrostatic potential surface of energy minimized geometry using AM1 technique) were used as independent variables along with suitable dummy parameters. The best equation describing A3 binding affinity [n=29, Q2=0.

Exploring QSAR of melatonin receptor ligand benzofuran derivatives using E-state index.

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.

QSAR modeling of globulin binding affinity of corticosteroids using AM1 calculations.

A quantitative structure-activity analysis of binding affinity of a series of 30 steroids for corticosteroid-binding globulin was performed using Wang-Ford charges of the non-hydrogen common atoms obtained from molecular electrostatic potential surface of AM1 optimized energy-minimized geometries of the compounds. Attempts were made to include lipophilicity (logP) and molar refractivity (MR) values of the whole molecules in the multivariate relations. The final relations were subjected to 'leave-one-out' cross-validation to check their predictive potential.

QSTR with extended topochemical atom indices. 2. Fish toxicity of substituted benzenes.

Considering the importance of quantitative structure-toxicity relationship (QSTR) studies in the field of aquatic toxicology from the viewpoint of ecological safety assessment, fish toxicity of various benzene derivatives has been modeled by the multiple regression technique using recently introduced extended topochemical atom (ETA) indices. The toxicity data have also been modeled using other selected topological descriptors and physicochemical variables, and the best ETA model has been compared to the non-ETA ones. Principal component factor analysis was used as the data preprocessing step to reduce the dimensionality of the data matrix and identify the important variables that are devoid of collinearities.

QSAR modeling of HIV-1 reverse transcriptase inhibitor 2-amino-6-arylsulfonylbenzonitriles and congeners using molecular connectivity and E-state parameters.

Anti-HIV-1 activity (assayed in MT-4 cell line) and HIV-1 reverse transcriptase (RT) binding affinity of 2-amino-6-arylsulfonylbenzonitriles and their thio and sulfinyl congeners (Chan et al., J. Med.

QSPR modeling of lipid-water partition coefficient by optimization of correlation weights of local graph invariants.

The optimization of correlation weights scheme was applied to model lipid-water partition coefficient (log P) of two sets of diverse functional aliphatic and aromatic compounds. In both cases, the optimized descriptors formulated based on the data of training sets generated statistically acceptable relations for the corresponding training sets, test sets, and combined sets. When the relations of log P values with the optimized molecular descriptors formulated based on the data of the training sets were used for calculation of log P values of the corresponding training sets, rpred2 values were found to be satisfactory (above 0.

Quantitative structure-activity relationship study on some azidopyridinyl neonicotinoid insecticides for their selective affinity towards the drosophila nicotinic receptor over mammalian alpha4beta2 receptor using electrotopological state atom index.

Neonicotinoids are the most important class of synthetic insecticides increasingly used in agriculture and veterinary medicine. Fundamental differences between the nicotinic acetylcholine receptors (nAChRs) of insects and mammals confer remarkable selectivity of the neonicotinoids at insect nAChR over mammalian nAChR. To identify pharmacophoric requirements of azidopyridinyl neonicotinoids for their efficacy and selectivity towards the insect nAChR over the mammalian one, quantitative structure-activity relationship (QSAR) study was performed using electrotopological state atom (ETSA) indices.