The North-East region of India is one of the twelve mega biodiversity region, containing many rare and endangered species. A curated database of medicinal and aromatic plants from the regions called NeMedPlant is developed. The database contains traditional, scientific and medicinal information about plants and their active constituents, obtained from scholarly literature and local sources. The database is cross-linked with major biochemical databases and analytical tools. The integrated database provides resource for investigations into hitherto unexplored medicinal plants and serves to speed up the discovery of natural productsbased drugs.AvailabilityThe database is available for free at http://bif.uohyd.ac.in/nemedplant/orhttp://202.41.85.11/nemedplant/

Peroxiredoxins(Prdx), the family of non-selenium glutathione peroxidases, are important antioxidant enzymes that defend our system from the toxic reactive oxygen species (ROS). They are thiol-based peroxidases that utilize self-oxidation of their peroxidatic cysteine (Cp) group to reduce peroxides and peroxidized biomolecules. However, because of its high affinity for hydrogen peroxide this peroxidatic cysteine moiety is extremely susceptible to hyperoxidation, forming peroxidase inactive sulfinic acid (Cys-SO2H) and sulfonic acid (Cys-SO3H) derivatives. With the exception of peroxiredoxin 6 (Prdx6), hyperoxidized sulfinic forms of Prdx can be reversed to restore peroxidase activity by the ATP-dependent enzyme sulfiredoxin. Interestingly, hyperoxidized Prdx6 protein seems to have physiological significance as hyperoxidation has been reported to dramatically upregulate its calcium independent phospholipase A2 activity. Using biochemical studies and molecular dynamic (MD) simulation, we investigated the roles of thermodynamic, structural and internal flexibility of Prdx6 to comprehend the structural alteration of the protein in the oxidized state. We observed the loosening of the hydrophobic core of the enzyme in its secondary and tertiary structures. These changes do not affect the internal dynamics of the protein (as indicated by root-mean-square deviation, RMSD and root mean square fluctuation, RMSF plots). Native-PAGE and dynamic light scattering experiments revealed the formation of higher oligomers of Prdx6 under hyperoxidation. Our study demonstrates that post translational modification (like hyperoxidation) in Prdx6 can result in major alterations of its multimeric status.

Both authors made equal contribution to the work.MEK-1 and MEK-2 are dual-specificity kinases and important components in the mitogen-activated protein kinase pathway. These enzymes are crucial for normal cell survival and are also expressed in several types of cancers, making them important targets for drug design. We have applied an integrated in silico approach that combines comparative molecular field analysis, comparative molecular similarity indices analysis, and molecular docking to study the structural determinants for the recognition of substituted isothiazole analogs as allosteric inhibitors against MEK-1 kinase. The best 3D-QSAR models for comparative molecular field analysis and comparative molecular similarity indices analysis were selected based on statistical parameters. 3D contour maps suggested that bulky or long-chain substitutions at the X position on the core part decrease the inhibitory activity, and the presence of a hydrogen bond donor substitution enhances the activity. The bulky and electronegative substitutions at the Y position on the core part enhance the activity of the inhibitors. Molecular docking studies reveal a large and hydrophobic pocket that accommodates the Y substitution and a polar pocket that accommodates substitutions on the X position and forms hydrogen bonding interactions with MEK-1 kinase. The results of the 3D-QSAR analysis corroborate with the molecular docking results, and our findings will serve as a basis for further development of better allosteric inhibitors of MEK-1 kinase against several cancers.Key words: allosteric inhibitor, comparative molecular field analysis, comparative molecular similarity indices analysis, MEK-1 kinase, molecular docking, substituted isothiazole analogs, three-dimensional quantitative structure-activity relationship In eukaryotes, signals from outside the cell to inside the nucleus are transduced by various growth factors, hormones, adaptor proteins, and enzymes to regulate normal cell survival, proliferation, and differentiation. The mitogen-activated protein kinase (MAPK) pathway that includes the Ras ⁄ Raf ⁄ MEK ⁄ extracellular-signal regulated kinase (ERK) signaling proteins is one of the important pathways in signal transduction. Ras is an upstream activator of several signaling pathways such as MAPK pathway. Kinase suppressor of Ras is an essential scaffolding protein that co-ordinates the assembly of Raf-MEK-ERK complexes (1-3). B-Raf and other upstream activator kinases phosphorylate and activate the MAP kinase ⁄ ERK kinases (MEK-1 and MEK-2) via serine phosphorylation. The activated MEK-1 and MEK-2 phosphorylate and activate the ERK1 and ERK2 MAPKs. MEK-1 and MEK-2 are dual specificity kinases that phosporylate both threonine and tyrosine residues on ERK1 and ERK2 (43-and 41-kDa MAP kinases, respectively) (4-6). In tumor cells, aberrant activation of the MAPK pathway owing to the mutations in Ras and Raf is frequently observed. Also, activated MAPK or elevated MAPK expression has been detected in a variety of human tumors, ...

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The enzyme β-1,3-glucan synthase, which catalyzes the synthesis of β-1,3-glucan, an essential and unique structural component of the fungal cell wall, has been considered as a promising target for the development of less toxic anti-fungal agents. In this study, a robust pharmacophore model was developed and structure activity relationship analysis of 42 pyridazinone derivatives as β-1,3-glucan synthase inhibitors were carried out. A five-point pharmacophore model, consisting of two aromatic rings (R) and three hydrogen bond acceptors (A) was generated. Pharmacophore based 3D-QSAR model was developed for the same reported data sets. The generated 3D-QSAR model yielded a significant correlation coefficient value (R2 = 0.954) along with good predictive power confirmed by the high value of cross-validated correlation coefficient (Q2 = 0.827). Further, the pharmacophore model was employed as a 3D search query to screen small molecules database retrieved from ZINC to select new scaffolds. Finally, ADME studies revealed the pharmacokinetic efficiency of these compounds.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-2589-3) contains supplementary material, which is available to authorized users.