Biomedical subjects

Nilanjan Roy

Publications and source records attributed to Nilanjan Roy.

9 recordsLinked to original sources

PubMed2006

Pharmacophoric features of Pseudomonas aeruginosa deacetylase LpxC inhibitors: an electronic and structural analysis.

Various electronic properties of structurally diverse synthetic LpxC inhibitors containing oxazoline, aroylserine and thiazoline rings were calculated and correlated with biological activity. These electronic features include the magnitude and locations of 3-dimensional molecular electrostatic potentials, hydrogen bond acceptor/donor density, lowest unoccupied molecular orbital, and highest occupied molecular orbital. Strong correlation of these stereo-electronic properties with LpxC inhibitory potency reveals the potential pharmacophoric features of specific LpxC inhibitors. Thus, these pharmacophoric features of LpxC inhibitors based on electronic and surface analysis could be successfully exploited for designing more potent LpxC inhibitors.

Amidohydrolases↗

PubMed2006

A novel range based QSAR study of human neuropeptide Y (NPY) Y5 receptor inhibitors.

A conventional QSAR study has been carried out using thermodynamic and other descriptors, on a set of arylsulfonamidomethylcyclohexyl derivatives as antagonists of potential obesity drug target human neuropeptide Y Y5 receptor. In addition, a novel range based method was applied to obtain a QSAR model so that the information contained in the compounds for which an approximate value instead of exact value of inhibitory activity was available could be included in the model. Analysis of models suggests that range based model is better in screening biologically active compounds from chemical library. The conventional model is able to predict activity accurately only for active compounds whereas the range based method is better in discriminating active and inactive compounds.

Anti-Obesity Agents↗

PubMed2006

Comparative protein modeling and surface analysis of Leishmania sirtuin: A potential target for antileishmanial drug discovery.

Homology model of Leishmania SIR2 shed new light on the ligand binding features of this enzyme. The molecular electrostatic potentials (MESP), the cavity depth analysis, and LmSIR2-hSIRT2 models' superposition suggested that the nicotinamide binding catalytic domain has several minor but potentially important structural differences. These differences could be exploited for designing antileishmanial compounds.

Amino Acid Sequence↗

PubMed2006

Cluster analysis and two-dimensional quantitative structure-activity relationship (2D-QSAR) of Pseudomonas aeruginosa deacetylase LpxC inhibitors.

Compounds from a wide variety of structural classes inhibit Pseudomonas aeruginosa deacetylase LpxC. However, a single unified understanding of the relationship between the structures and activities of these compounds still eludes the researchers. We report herein, the development of cluster analysis-based 2D-QSAR models for LpxC inhibition. Principal component analysis (PCA), hierarchical cluster analysis (HCA), and genetic function approximation (GFA) were employed for the development of the QSAR model. The conventional 2D-QSAR model derived for the complete set of three-structural classes had unsatisfactory predictability with a correlation coefficient (r(2)) of 0.703 and a cross-validated correlation coefficient (q(2)) of 0.584. Descriptor-based cluster analysis indicated that the three-structural classes of LpxC inhibitors studied belonged to two clusters. Separate QSAR models for these two clusters showed substantially improved predictability with r(2) values of 0.904 and 0.944 and q(2) values of 0.805 and 0.906, respectively. Thus, we expect that compared to the conventional model, our two QSAR models can be better used to preliminarily screen molecules from a diverse chemical space while searching for novel LpxC inhibitors.

Amidohydrolases↗

PubMed2006

Quantitative structure activity relationship studies of aryl heterocycle-based thrombin inhibitors.

A quantitative structure activity relationship (QSAR) analysis has been performed on a data set of 42 aryl heterocycle-based thrombin inhibitors. Several types of descriptors including topological, spatial, thermodynamic, information content and E-state indices were used to derive a quantitative relationship between the anti thrombin activity and structural properties. Genetic algorithm based genetic function approximation method of variable selection was used to generate the model. Best model was developed when number of descriptors in the equation was set to five. Highly statistically significant model was obtained with atom type logP descriptors, logP and Shadow_YZ. The model is not only able to predict the activity of new compounds but also explained the important regions in the molecules in a quantitative manner.

Anticoagulants↗

PubMed2006

Meta-analysis of glutathione S-transferase M1 genotype and risk toward head and neck cancer.

BACKGROUND: We sought to evaluate the estimated risk of GSTM1 null genotype and squamous cell carcinoma of the head and neck (SCCHN). METHODS: The studies done so far for GSTM1 null genotype as a risk factor associated with head and neck cancer are not conclusive and have shown conflicting results. A meta-analysis has been carried out on 22 case-control studies collected from the literature. Precision of the risk estimate and presence of publication bias in those studies are also evaluated by funnel plot analysis. RESULTS: A total of 3527 cases and 4211 controls constitute the subjects of meta-analysis. The principal outcome measured was the odds ratio (OR) for the risk of head and neck cancer. Pooling the studies together, the OR was 1.50 (95% confidence interval [CI], 1.21-1.87). When stratified according to Asians and Caucasians, the OR increased in the Asians (OR, 1.93; 95% CI, 1.29-2.90), suggesting that the risk is more pronounced in Asians. However, a substantial amount of publication bias is also associated with studies conducted on the Asian population. CONCLUSION: A review of the 22 case-control studies for risk of SCCHN and GSTM1 null genotype indicate that greater attention should be paid to designing future studies so that a more precise risk estimate can be achieved.

Asian People↗

PubMed2005

Mrg19 depletion increases S. cerevisiae lifespan by augmenting ROS defence.

Caloric restriction (CR) is the most compelling example of lifespan extension by external manipulation. Although the molecular mechanisms remain unknown, the theory of hormesis has been invoked to explain the life promoting effects of CR. Hormesis is defined as the beneficial effects of low intensity stressor on a cell or organism. Mrg19 is a putative transcription factor that regulates carbon and nitrogen metabolism in yeast. In this study, we have found that deletion of MRG19 gene causes metabolic shift in yeast cells, leading to higher intracellular reactive oxygen species, augmentation of scavenging enzymes and longer lifespan compared to wild-type cells. All these results together suggest that similar to CR, depletion of Mrg19 leads to a condition of mild stress which in turn enhances vitality.

Caloric Restriction↗

PubMed2005

Caloric restriction augments ROS defense in S. cerevisiae, by a Sir2p independent mechanism.

Aging is associated with increased production of reactive oxygen species (ROS) and oxidation-induced damage to intracellular structures and membranes. Caloric restriction (CR) has been demonstrated to delay aging in a variety of species. Although the mechanisms of CR remain to be clearly elucidated, reductions in oxidative damage have been shown to increase lifespan in several model systems. Contrary to the general belief that ROS production is reduced in CR, this article provides evidence that not only oxygen consumption but ROS production is enhanced in the calorie restricted condition. To understand the biological mechanism underlying the anti aging action of CR, the role of scavenging enzymes was studied. It was found that super oxide dismutase (SOD1 and SOD2), catalase and glutathione peroxidase (GPx) all are over expressed in CR. We further investigated the role of Sir2, a potential effector of CR response in the activation of scavenging enzymes. No marked difference was found in CR mediated activation of SOD and catalase in the absence of Sir2. Our results suggest that in CR scavenging enzymes are activated by a Sir2 independent manner.

Caloric Restriction↗

PubMed2003

Sir3p phosphorylation by the Slt2p pathway effects redistribution of silencing function and shortened lifespan.

An organism's lifespan is modulated by environmental conditions. When nutrients are abundant, the metabolism of many organisms shifts to growth or reproduction at the expense of longer lifespan, whereas a scarcity of nutrients reverses this shift. These correlations suggest that organisms respond to environmental changes by altering their metabolism to promote either reproduction and growth or long life. The only previously reported signaling mechanism involved in this response is the nutrient-responsive insulin/insulin-like growth factor-1 receptor pathway. Here we report another pathway that controls the length of yeast lifespan. Commitment to cell growth activates the Slt2p MAP kinase pathway, which phosphorylates the transcriptional silencing protein Sir3p, resulting in a shorter lifespan. Elimination of the Sir3p phosphorylation site at Ser275 extended lifespan by 38%. Lifespan extension occurs by a mechanism that is independent of suppressing rDNA recombination. Thus, Slt2p is an enzymatic regulator of silencing function that couples commitment to cell growth and shorter lifespan.

Alleles↗