Earticle

New 4,4’-[6-(o-carboranylalkoxy)-1,3,5-triazine-2,4-diyl]dimorpholine derivatives have been prepared by reacting 4,4’- [6-(alkynyloxy)-1,3,5-triazine-2,4-diyl]dimorpholines with decaborane and N,N-dimethylaniline as base. The intermediate compounds, 4,4’-[6-(alkynyloxy)-1,3,5-triazine-2,4-diyl]dimorpholines, have been prepared by reacting 4,4’-[6-chloro- 1,3,5-triazine-2,4-diyl]dimorpholines with prop-2-yn-1-ol, but-3-yn-1-ol, and pet-4-yn-1-ol, and potassium tert-butoxide (t- BuOK) as base. The structure of these compounds has been confirmed by IR, 1H, 11B, and 13C NMR and X-ray crystallographic studies.

The red algae Gracilaria vermiculophylla is widely spread around seaside areas across the globe, and has been used as a food resource in Southeast Asian countries. Previous studies have shown that Gracilaria red algae extracts have beneficial antihypercholesterolemic, antioxidant, anti-inflammatory, and antimicrobial effects. In this study, we investigated the antioxidant effects of Gracilaria vermiculophylla extracts (GV-Ex) on human bone marrow mesenchymal stem cells (hBM-MSCs). The acetone and DMSO/ethanol solvents of the tested GV contain higher total flavonoid and polyphenolic contents that can strongly scavenge reactive oxygen species (ROS). Pre-treatment with GV-Ex protected hBM-MSCs against oxidative stress induced by hydrogen peroxide treatment. The protective effects of GV-Ex treatment were confirmed by MTT assay. The elevated levels of ROS in hBM-MSCs caused by hydrogen peroxide induced oxidative stress were significantly decreased by GV extract treatment. The levels of the antioxidant proteins superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), and catalase (CAT) were also restored or protected by GV-Ex treatment, suggesting that GV extracts moderate excess ROS levels and prevent cells from oxidative damage.

Robust design is an approach to reducing performance variation of quality characteristic values in quality engineering. Product array approach which is used in the Taguchi parameter design has a number of advantages by considering the noise factor. Taguchi has an idea that mean and variation are handled simultaneously to reduce the expected loss in products and processes. Taguchi has used the signal-to-noise ratio (SN) to achieve the appropriate set of operating conditions where variability around target is low in the Taguchi parameter design. Many Statisticians criticize the Taguchi techniques of analysis, particularly those based on the SN. In this paper we propose a substantially simpler optimization procedure for robust design using desirability function without resorting to SN.

We show that the (Castelnuovo-Mumford) regularity of a homogeneous Cohen-Macaulay ring agrees with some of the invariants defined the papers, and we study a ring of small index.

5-Hydroxytryptamine receptor 7 (5-HT7R) is one of G-Protein coupled receptors, which is found to be involved in the pathophysiology of various neurological disorders including depression, sleep disorders, memory deficiency and neuropathic pain. After activation of 5-HT7R by serotonin, it activates the production of the intracellular signaling molecule cyclic AMP. The availability of 3D structure of the receptor would enhance the development of new drugs. Hence, in the present study, homology modelling of human 5-hydroxytryptamine receptor 7 (5-HT7R) was performed using comparative modelling (Easy Modeller) and threading (I-TASSER) approaches. The generated models were validated using Ramachandran plot and ERRAT plot and the best models were selected based on the validation results. The 3D model developed here could be useful for identifying crucial residues and further docking study.

Caspases, a family of cysteinyl aspartate–specific proteases plays a central role in the regulation and the execution of apoptotic cell death. Caspase-3 has been proven to be an effective target for reducing the amount of cellular and tissue damage because the activation of caspases-3 stimulates a signalling pathway that ultimately leads to the death of the cell. In this study, Hologram based Quantitative Structure Activity Relationship (HQSAR) models was generated on a series of Caspase-3 inhibitors named 3, 4-dihydropyrimidoindolones derivatives. The best HQSAR model was obtained using atoms, bonds, and hydrogen atoms (A/B/H) as fragment distinction parameter using hologram length 61 and 3 components with fragment size of minimum 5 and maximum 8. Significant cross-validated correlation coefficient (q2= 0.684) and non cross-validated correlation coefficients (r2= 0.754) were obtained. The model was then used to evaluate the eight external test compounds and its r2 pred was found to be 0.559. Contribution map show that presence of pyrrolidine sulfonamide ring and its bulkier substituent’s makes big contributions for improving the biological activities of the compounds.

Corticotropin - releasing hormone receptor 1 (CRHR1) forms an integral part of the pathophysiology of disorders like post-traumatic stress disorder, stress, anxiety, addiction, and depression. Hence it is essential to look for new, potent and structure-specific inhibitors of CRHR1. We have analysed the protein-protein interaction complexes of the CRHR1 receptor with its native ligand CRF and full agonist Sauvagine. The structure of Sauvagine was predicted using homology modelling. We have identified that the residues TYR253, ASP254, GLU256, GLY265, ARG1014 and LY1060 are important in the formation of protein-protein complex formation. Future studies on these residues could throw light on the crucial structural features required for the formation of CRHR1-inhibitor complex and in studies that try to solve the structural complexities of CRHR1.

p38 MAP kinase belongs to the Mitogen-activated protein (MAP) kinase family; a serine/threonine kinase. It plays an important role in intracellular signal transduction pathways. It is associated with the development and progression of various cancer types making it a crucial drug target. Present study involves the HQSAR analysis of recently reported imidazo[1,2-b]pyridazine derivatives as p38 MAP kinase antagonists. The model was generated with Atom (A), bond (B), chirality (Ch), and hydrogen (H) parameters and with different set of atom counts to improve the model. An acceptable HQSAR model (q2=0.522, SDEP=0.479, NOC=5, r2=0.703, SEE=0.378, BHL=97) was developed which exhibits good predictive ability. A contribution map for the most active compound (compound 17) illustrated that hydrogen and nitrogen atoms in the ring A and ring B, as well as nitrogen atom in ring C and the hydrogen atom in the ring D provided positive activity in inhibitory effect while, the least active compound (compound 05) possessed negative contribution to inhibitory effect. Hence, analysis of produced HQSAR model can provide insights in the designing potent and selective p38 MAP kinase antagonists.

This study was planned to prepare the high strength hydrogel ophthalmic lens containing isocyanate group and nanoparticles. HDI with carbon nanoparticles were used as additives for the basic combination of HEMA, MA and MMA, and the materials were copolymerized with EGDMA as the cross-linking agent and AIBN as the initiator. The mixture was heated at 100oC for an hour to produce the high performance hydrogel ophthalmic lens by cast mold method. Measurement of the physical characteristics of the produced material showed that the refractive index was in the range of 1.4027~1.4600, water content 25.21~44.01%, contact angle 54.18~72.94°, visible light transmittance 53.03~92.09%, and tensile strength 0.1024~0.2359 kgf and breaking strength was 0.0872~0.2825 kgf. The results showed an increase of refractive index while the decrease in water content. And also, the breaking strength was highest when the addition ratio of HDI was 5%(wt). As a result of the absorbance measurement, no significant difference was observed in all the samples, so it can be judged that the stabilization of nanoparticles in the polymer was maintained.

CXCR6 is a major target in drug design as it is a determinant receptor in many diseases like AIDS, Type I Diabetes, some cancer types, atherosclerosis, tumor formation, liver disease and steatohepatitis. In this study, we propose the active site residues of CXCR6 molecule. We employed homology modelling and molecular docking approach to generate the 3D structure for CXCR6 and to explore its interaction between the antagonists and agonists. 3D models were generated using 14 different templates having high sequence identity with CXCR6. Surflex docking studies using pyridine and pyrimidine derivatives enabled the analysis of the binding site and finding of the important residues involved in binding. 3D structure of CXCL16, a natural ligand for CXCR6, was modelled using PHYRE and protein – protein docking was performed using ClusPro. The residues which were found to be crucial in interaction with the ligand are THR110, PHE113, TYR114, GLN160, GLN195, CYS251 and SER255. This study can be used as a guide for therapeutic studies of human CXCR6.