PubMed Health⌕ Search

Biomedical subjects

Hiroshi Chuman

Publications and source records attributed to Hiroshi Chuman.

At least 19 recordsLinked to original sources
PubMed2006

An integrated database of flavonoids.

Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Some of these molecules exhibit various physiological activities. Among existing drugs, there are a huge number of compounds bearing a flavonoid-related skeleton. Because of the relevance for pharmaceutical research, it would be beneficial to collect these compounds into a database. Recently, various databases of chemicals were compiled to help biological and/or chemical research, but no comprehensive database of flavonoids with chemical structures and physicochemical parameters, supposedly related to their activity, is available yet. The aim of this research was to merge the information about flavonoids of plant origin and flavonoids used as medicines into a database. Moreover, predictions of activities against various targets were performed using a virtual screening procedure to demonstrate a possible application of the database for pharmaceutical research.

Chemistry, Physical↗
PubMed2006

Effect of a conjugated quercetin metabolite, quercetin 3-glucuronide, on lipid hydroperoxide-dependent formation of reactive oxygen species in differentiated PC-12 cells.

To assess the efficacy of conjugated quercetin metabolites as attenuators for oxidative stress in the central nervous system, we measured the 13-hydroperoxyoctadecadienoic acid (13-HPODE)-dependent formation of reactive oxygen species (ROS) in pheochromocytoma PC-12 cells in the presence of quercetin 3-O-beta-glucuronide (Q3GA) and related compounds. A 2',7'-dichlorofluorescin (DCFH) assay showed that Q3GA significantly suppressed the formation of ROS, when it was coincubated with 13-HPODE (coincubation system). However, it was less effective than quercetin aglycon in the concentration range from 0.5 to 10 microM. In an experiment in which the cells were incubated with the test compounds for 24 h before being exposed to 13-HPODE, Q3GA was also effective in suppressing the formation of ROS in spite that little Q3GA was taken up into the cells. These results suggest that antioxidative metabolites of quercetin are capable of protecting nerve cells from attack of lipid hydroperoxides.

Animals↗
PubMed2005

Determination of lipophilicity by reversed-phase high-performance liquid chromatography. Influence of 1-octanol in the mobile phase.

Lipophilicity was evaluated using a novel RP-HPLC stationary phase (Discovery-RP-Amide-C16) with and without 1-octanol added to the mobile phase. A set of 46 drugs and flavonoids characterized by a broad structural diversity and a wide log Poct range (-0.69 to 5.70) was selected for this study. This set consists of neutral solutes and solutes with acidic or ampholytic functionalities which were maintained neutral at pH 2.5 or 4. In our conditions, the addition of 1-octanol in the mobile phase proved a key factor to derive a lipophilicity index log k(w) highly correlated with log Poct for all investigated solutes. 1-Octanol improved the correlation between log Poct and log k(w) mainly by influencing the retention behavior of the solutes with log Poct values below +3. This study brings additional evidence that under proper experimental conditions of stationary and mobile phases, RP-HPLC is a very useful method to obtain log Poct values.

1-Octanol↗
PubMed2005

Comparative study on solvation free energy expressions in reference interaction site model integral equation theory.

The performance of the recently proposed partial wave (PW) free energy functional is compared with those of two previous expressions, Gaussian fluctuation (GF) and hypernetted chain (HNC), within the reference interaction site model framework. The applications to the calculations of ambient and supercritical water, solvation free energies of organic molecules, and partition coefficients clearly show that the PW and GF free energy expressions provide more reliable results than the HNC functional, indicating rather associative situations of geometry in ordinary liquids of medium-sized molecules.

Models, Theoretical↗
PubMed2005

Connecting traditional QSAR and molecular simulations of papain hydrolysis--importance of charge transfer.

Molecular dynamics and full structure LocalSCF semi-empirical quantum mechanics calculations of receptor-ligand complexes were carried out to investigate structure-activity relationship for the papain hydrolysis of a series of N-benzoylglycine esters and reinterpret traditional QSAR descriptors using detailed structural information. A correlation of r(2)=0.694 was obtained and it was shown that the pattern of charge distribution on the ester group is different if charges of free or complex ligands or are analyzed. The results can help to understand how traditional QSAR descriptors, such as F or sigma, interacts with other electronic effects during complex formation.

Computer Simulation↗
PubMed2005

Application of a stepwise flow ratiometry without phase separation to the determination of the chloroform/water distribution coefficients of volatile diazines.

The chloroform/water distribution coefficients (K(D)) of sixteen diazine compounds were determined by a stepwise flow ratiometry. An aqueous solution of analyte was delivered and merged with chloroform. The flow rate ratio of both the phases was varied stepwise under a constant total (chloroform+aqueous) flow rate. The analyte was extracted to chloroform while both the phases, which were segmented by each other, were passing through an extraction coil. The segmented stream was then led to a UV/Vis detector directly without phase-separation. The absorbance of the chloroform and aqueous phases (A(o) and A(a), respectively) was each measured at the maximum absorption wavelength of the analyte. The plots of A(-1) against R(f), (AR(f))(-1) against R(f)(-1), and AR(f) against A gave straight lines, where A was A(o), A(a) or the sum of them (A(S)). The K(D) of the analyte was calculated from the slopes and intercepts of the plots. The log K(D) values obtained for the analytes (-0.5-1.4) were agreed well with the values measured by a shake-flask method. The present method is simple, rapid (5 min/determination) and applicable to the volatile compounds with reasonable precision (standard deviation of log K(D)<0.07).

Chemical Phenomena↗
PubMed2005

Approach to novel functional foods for stress control: 1. Toward structure-activity relationship and data mining of food compounds by chemoinformatics.

Over the past several decades, thousands of natural organic compounds have been isolated from foods, and the information about their structures and biological activities has been accumulated. Despite the long research history of food products and their potential great promise as a medicine and functional food, the systematic research and development have not been carried out extensively. For understanding of the comprehensive structure-activity relationship, we have developed the database system of flavonoids, which are frequently found in vegetables and fruits. We also plan to execute a virtual screening of flavonoids with antidepressant activity by using the database and an advanced chemoinformatic tool. In this section, we will briefly describe (1) flavonoid database and (2) virtual screening of antidepressant compounds.

Antidepressive Agents↗
PubMed2005

Construction of a novel database for flavonoids.

Flavonoids are polyphenolic compounds that exist ubiquitously in foods of plant origin. Flavonoids show various interesting biological activities, such as removal of oxygen radical, anti-cancer action, improvement of high blood pressure, antibacterial, antibiotic and anti-allergy actions. So far, over 4000 structurally unique flavonoids have been isolated from plant sources. Recently, databases of chemicals have been utilized in to help chemical and biological researches, however the comprehensive database of flavonoids with information about structural, biological and physicochemical properties not yet available. We have constructed the integrated database of flavonoids for nutrition research.

Chemical Phenomena↗
PubMed2005

Virtual screening models for finding novel antidepressants.

Virtual screening was carried out against various biological targets related to depression by support vector machine classification using the atom-type descriptors. The models were effective as over 75 and 95% of the molecules in external test datasets could be correctly classified, depending on target. Antidepressant compounds had predicted activity against 2.3 targets, on average. An introduction is given to virtual screening and the results of classification experiments are presented.

Algorithms↗
PubMed2004

Analyses of the partition coefficient, log P, using ab initio MO parameter and accessible surface area of solute molecules.

To analyze the log P(sol/w) values (sol: n-octanol or chloroform, w: water) in the framework of the molecular orbital (MO) procedure, we selected solute descriptors such as the solvation energy difference between aqueous and organic solvent phases and the "surface" area of solute molecules to which water molecules are accessible. The solvation energy of solute molecules in their minimum free-energy conformation was calculated using the ab initio self-consistent reaction field-MO method with the conductor-like screening model. The experimentally measured log P(sol/w) value of various solutes except for those of amphiprotics was shown to be analyzable reasonably well by the MO model with additional descriptors for the hydrogen-bonding patterns in the solute-solvent interactions.

1-Octanol↗
PubMed2004

Stress control and human nutrition.

Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation.

Antioxidants↗
PubMed2002

How does the mitochondrial ADP/ATP carrier distinguish transportable ATP and ADP from untransportable AMP and GTP?Dynamic modeling of the recognition/translocation process in the major substrate binding region.

To understand the transport mechanism of the bovine heart mitochondrial ADP/ATP carrier at the atomic level, we studied the four-dimensional features of the interaction of various purine nucleotides with the adenine nucleotide binding region (ABR) consisting of Arg(151)-Asp(167) in the second loop facing the matrix side. After three-dimensional modeling of ABR based on the experimental results, its structural changes on interaction with purine nucleotides were examined by molecular dynamics computation at 300 K. ATP/ADP were translocated to a considerable degree from the matrix side to the inner membrane region accompanied by significant backbone conformational changes, whereas neither appreciable translocation nor a significant conformational change was observed with the untransportable nucleotides AMP/GTP. The results suggested that binding of the terminal phosphate group and the adenine ring of ATP/ADP with Arg(151) and Lys(162), respectively, and subsequent interaction of a phosphate group(s) other than the terminal phosphate with Lys(162) triggered the expansion and subsequent contraction of the backbone conformation of ABR, leading to the translocation of ATP/ADP. Based on a simplified molecular dynamic simulation, we propose a dynamic model for the initial recognition process of ATP/ADP with the carrier.

Adenosine Diphosphate↗
PubMed2002

Quantitative estimation of interaction between carbohydrates and concanavalin A by surface plasmon resonance biosensor.

We measured the affinity of more than 20 sugars with concanavalin A (ConA) by an optical biosensor (surface plasmon resonance sensor) using asialofetuin (ASF) as an immobilized binding partner of ConA. We determined kinetic parameters of the effects of sugars on the dissociation of ConA from ASF quantitatively, and the structural requirements of the functional groups of sugars for binding with ConA. We found that the affinity of ConA for sugars is dependent on its conformation induced by interaction with the binding partner. In addition, the results showed that optical biosensor system is well mimics the interaction of ConA with sugars in biomembrane.

Animals↗
PubMed2002

Prediction of the 1-octanol/H2O partition coefficient, log P, by ab initio MO calculations: hydrogen-bonding effect of organic solutes on log P.

To predict the 1-octanol/H2O partition coefficient, log P, based on molecular structures, we calculated the solvent accessible surface area and the solvation energy difference of 166 organic molecules between 1-octanol and water environments with the ab initio molecular orbital self-consistent reaction field method, and then analyzed the relationships among the measured log P values with these two structural quantities by multiple linear-regression analyses. Physicochemically meaningful correlations were obtained, suggesting that non-hydrogen bonding and hydrogen-acceptor molecules behave similarly to each other in partitioning, but that hydrogen-donor molecules behave differently from the former molecules. The results provide a new computational approach for predicting log P.

Journal Article↗
PubMedDate not supplied

VISCANA: visualized cluster analysis of protein-ligand interaction based on the ab initio fragment molecular orbital method for virtual ligand screening.

We have developed a visualized cluster analysis of protein-ligand interaction (VISCANA) that analyzes the pattern of the interaction of the receptor and ligand on the basis of quantum theory for virtual ligand screening. Kitaura et al. (Chem. Phys. Lett. 1999, 312, 319-324.) have proposed an ab initio fragment molecular orbital (FMO) method by which large molecules such as proteins can be easily treated with chemical accuracy. In the FMO method, a total energy of the molecule is evaluated by summation of fragment energies and interfragment interaction energies (IFIEs). In this paper, we have proposed a cluster analysis using the dissimilarity that is defined as the squared Euclidean distance between IFIEs of two ligands. Although the result of an ordered table by clustering is still a massive collection of numbers, we combine a clustering method with a graphical representation of the IFIEs by representing each data point with colors that quantitatively and qualitatively reflect the IFIEs. We applied VISCANA to a docking study of pharmacophores of the human estrogen receptor alpha ligand-binding domain (57 amino acid residues). By using VISCANA, we could classify even structurally different ligands into functionally similar clusters according to the interaction pattern of a ligand and amino acid residues of the receptor protein. In addition, VISCANA could estimate the correct docking conformation by analyzing patterns of the receptor-ligand interactions of some conformations through the docking calculation.

Binding Sites↗
PubMedDate not supplied

Screening for new antidepressant leads of multiple activities by support vector machines.

Virtual screening was carried out against 21 biological targets related to depression by support vector machine classification using the same atom-type descriptors. The models were effective as 0.2-0.8 of theoretical enrichments of the external test data sets could be achieved, depending on the target. The set of predicted active molecules had large diversity and contained examples with high dissimilarity to the compounds of training sets. Filtering the database of known antidepressants by all 21 models it was found that on average compounds were classified active for 2.3 targets.

Antidepressive Agents↗