Stereoselective synthesis of 1'-functionalized-4'-thionucleosides

Stereoselective functionalization of the 1'-position of 4'-thionucleosides was achieved using a stereoselective S(N)2 reaction controlled by 5-membered ring coordination.     

Molecular Modelling and Insilico Engineering of PapMV-CP Towards Display and Development of Capripox Viral Like Particles Based on Immunogenic P32 Envelop Protein is the Homologous of the Vaccinia-Viral H3L Gene: An Insilico Approach

International Journal of Peptide Research and Therapeutics - Viral-like particles are assembled from capsid protein structural subunits of different viruses and have ability to establish research...     

Design, synthesis, and anti-tumor activity of 4'-thionucleosides as potent and selective agonists at the human A3 adenosine receptor

On the basis of potent and selective binding affinity of Cl-IB-MECA to the human A(3) adenosine receptor, its 4'-thioadenosine derivatives were efficiently synthesized starting from D-gulonic gamma-lactone. Among compounds tested, 2-chloro-N(6)-(3-iodobenzyl)- and 2-chloro-N(6)-methyl-4' -thioadenosine-5' -methyluronamides (7a and 7b) exhibited nanomolar range of binding affinity (K(i) = 0.38 nM and 0.28 nM, respectively) at the human A(3)AR. These compounds showed anti-growth effects on HL-60 leukemia cell, which resulted from the inhibition of Wnt signaling pathway.     

Synthesis of D- and L-apio nucleoside analogues with 2'-hydroxyl group as potential anti-HIV agents

The present work describes the asymmetric synthesis of D- and L-apio-2',3'-dideoxynucleoside analogues, 4 and 5 with 2'-hydroxyl group via a common intermediate 9, starting from D-galactose. Stereoselective dihydroxylation and deoxygenation through radical inversion were successfully employed to synthesize the key intermediate 12 with D-apio structure, while stereoselecetive hydroboration-oxidation was used for the synthesis of another key intermediate 18 with L-apio structure.     

Stereoselective synthesis of novel thioiso dideoxy nucleosides with exocyclic methylene as potential antiviral agents

Novel thioiso pyrimidine and purine nucleosides substituted with exocyclic methylene have been synthesized, starting from D-xylose. Cyclization of the dimesylate to the 4-thiosugar 6a proceeded in pure SN2 reaction in the presence of allylic functional group.     

Efficiency of Coleus aromaticus extract in modifying cyclophosphamide and mitomycin-C induced clastogenicity in mouse bone marrow cells

The anticlastogenic potency of the ethanolic extract of a medicinal plant, C. aromaticus was investigated by taking bone marrow chromosomal aberration assay and micronucleus (MN) test as the test parameters. Swiss albino mice were fed orally with different doses (10,15, 25, 50 and 100 mg/kg body weight) of ethanolic extract for 7 days and on the 7th day, two doses each of anticancer drugs cyclophosphamide (CP; 25 and 50 mg/kg body weight) and mitomycin-C (MMC; 4 and 8 mg/kg body weight) were injected, ip, to different groups of animals. Bone marrow MN preparations were made at 24 and 48 hr time intervals. Coleus extract reduced CP and MMC induced MN and lower doses of the extract were found to be more effective than higher doses. The effective doses of extract in MN test were selected to study the anticlastogenic effects against CP (25 and 50 mg/kg body weight) and MMC (2 and 4 mg/kg body weight) induced chromosomal aberrations. The results indicate the protective effect of C. aromaticus against CP and MMC induced cytogenetic damage.     

Computational investigations on the hemodynamic performance of a new swirl generator in bifurcated arteries

Hemodynamic behaviour of blood in the bifurcated arteries are closely related to the development of cardiovascular disease. The secondary flows generated at the bifurcation zone promotes the deposition of atherogenic particles on the outer walls. The present study aims at suppressing the development of atherosclerosis plaque by inducing helical flow structure in the arterial passage. To realize this objective a novel swirl generator (stent like structure with an internal groove) has been developed to induce helicity in the bifurcated passage. The functional requirement of the swirl generator is to minimize the relative residence time (RRT) of the fluid layer near the endothelial wall without generating any additional pressure drop. Different configurations of the swirl generator have been tested computationally using large eddy simulation (LES) model. It is observed that the induced helical flow redistributes the kinetic energy from the centre to the periphery. A single rib swirl flow generator proximal to the stent treated passage can generate sufficient helicity to bring down the RRT by 36% without generating any additional pressure drop. The swirl flow adds azimuthal instability which increase vortex formations in the passage. The induced helical flow in the domain provokes more linked vortices, which may act as self-cleaning mechanism to the arterial wall.     

Predicting anti-cancer activity of quinoline derivatives: CoMFA and CoMSIA approach

The 3D quantitative structure-activity relationships of 31 quinoline nuclei containing compounds and their biological activity have been investigated to establish various models. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies resulted in reliable and significant computational models. The obtained CoMFA model showed high predictive ability with q(2) = 0.592, r(2) = 0.966 and standard error of estimation (SEE) = 0.167, explaining majority of the variance in the data with two principal components. Predictions obtained with CoMSIA steric, electrostatic, hydrophobic, hydrogen-bond acceptor and donor fields (q(2) = 0.533, r(2) = 0.985) showed high prediction ability with minimum SEE (0.111) and four principal components. The information obtained from the CoMFA and CoMSIA contour maps can be utilized for the design and development of topoisomerase-II inhibitors for synthesis.     

Molecular interaction of fenvalarate with actin

The structure of α-Cyano-3-phenoxybenzyl-2-(4-chlorophenyl)-3-methylbutyrate (Fenvalarate) has been established by X-ray crystallography to understand the structure-activity relationship, which is of paramount importance in the toxicological studies of the compound. Fenvalarate is stabilized by intermolecular C-H…O, C-H…Cl, C-H…π and C-H…N interactions which are responsible for the stability of the compound and its interaction with the Actin. The crystallographic coordinates of the compound was extrapolated to docking studies to elucidate the action of fenvalarate against neural cytoskeletal protein of insect and mammalian β-actin. A strong affinity was observed in binding of fenvalarate with insect β-actin (-7.71kcal/mol, Ki = 2.23μM) indicating it as a potent insecticide and moderate toxicity towards mammalian β-actin (-7.07kcal/mol, Ki=6.54μM).