Microwave Activated Solid Support Synthesis of New Antibacterial Quinolones

Summary.  A novel synthesis of 6-fluoro-7-(5-aryl-1,3,4-thiadiazol/oxadiazol-2-yl-sulfanyl)-4-quinolone-3-carboxylic acids from 7-chloro-6-fluoro-4-quinolone-3-carboxylic acid and 5-substituted 1,3,4-thiadiazoles/oxadiazoles on basic alumina under microwave activation is described. All compounds were screened for their in vitro antibacterial activity against B. lichenformis, 2689, K. aerogens 2281, S. typhimurium 2501, E. herbicola 2491, and P. vulgaris 2027 and found to possess activities comparable to that of the standard drug norfloxacin. Received May 2, 2000. Accepted (revised) June 13, 2000     

Spectrophotometric Estimation of Citral in Essential Oil

Citral forms an important constituent of many essential oils. It is present in a large number of essential oils containing lemon perfume and is of great commercial value. Methods of estimation of citral, available in literature are not very accurate or time consuming. The method developed by the author is based on colour change reaction of citral with rhodium (III). If all necessary requirements for experiment are ready, the estimation of citral occures within ten minutes. Rhodium (III) can also be determined with its colour change reaction by citral.     

Charge in cosmological models

The balanced field equations due to Penney are used to find solutions for cosmological models in the presence of charge. Herein, it is found that the introduction of charge adds additional terms to the Einstein conservation equation and distribution expressions. The curvature parameter is affected and it is concluded that whereas matter affects it positively, the charge does so negatively. There then arises also the possibility of an evolution of local systems against the background of a global expansion.     

Chemoenzymatic glycan-selective remodeling of a therapeutic lysosomal enzyme with high-affinity M6P-glycan ligands. Enzyme substrate specificity is the name of the game

Functionalization of therapeutic lysosomal enzymes with mannose-6-phosphate (M6P) glycan ligands represents a major strategy for enhancing the cation-independent M6P receptor (CI-MPR)-mediated cellular uptake, thus improving the overall therapeutic efficacy of the enzymes. However, the minimal high-affinity M6P-containing N-glycan ligands remain to be identified and their efficient and site-selective conjugation to therapeutic lysosomal enzymes is a challenging task. We report here the chemical synthesis of truncated M6P-glycan oxazolines and their use for enzymatic glycan remodeling of recombinant human acid α-glucosidase (rhGAA), an enzyme used for treatment of Pompe disease which is a disorder caused by a deficiency of the glycogen-degrading lysosomal enzyme. Structure–activity relationship studies identified M6P tetrasaccharide oxazoline as the minimal substrate for enzymatic transglycosylation yielding high-affinity M6P glycan ligands for the CI-MPR. Taking advantage of the substrate specificity of endoglycosidases Endo-A and Endo-F3, we found that Endo-A and Endo-F3 could efficiently deglycosylate the respective high-mannose and complex type N-glycans in rhGAA and site-selectively transfer the synthetic M6P N-glycan to the deglycosylated rhGAA without product hydrolysis. This discovery enabled a highly efficient one-pot deglycosylation/transglycosylation strategy for site-selective M6P-glycan remodeling of rhGAA to obtain a more homogeneous product. The Endo-A and Endo-F3 remodeled rhGAAs maintained full enzyme activity and demonstrated 6- and 20-fold enhanced binding affinities for CI-MPR receptor, respectively. Using an in vitro cell model system for Pompe disease, we demonstrated that the M6P-glycan remodeled rhGAA greatly outperformed the commercial rhGAA (Lumizyme) and resulted in the reversal of cellular pathology. This study provides a general and efficient method for site-selective M6P-glycan remodeling of recombinant lysosomal enzymes to achieve enhanced M6P receptor binding and cellular uptake, which could lead to improved overall therapeutic efficacy of enzyme replacement therapy.

An efficient one-pot M6P glycan remodeling of a multiply glycosylated lysosomal enzyme (Lumizyme) affords a new glycoengineered protein that shows greatly improved receptor binding, cellular uptake, and degradation of lysosomal glycogen in an in vitro model of Pompe disease.     

Stereoselective total synthesis of Jaspine B (Pachastrissamine) utilizing iodocyclization and an investigation of its cytotoxic activity

The stereoselective synthesis of Jaspine B has been achieved from easily available (S)-Garner’s aldehyde. The trisubstituted tetrahydrofuran core of Jaspine B was constructed by utilizing a diastereoselective iodocyclization as the key step. Deiodination and debenzylation were performed in a single step by using n-Bu₃SnH and ABCN as a conjugate catalyst system. The in vitro cytotoxicity of compounds 1 and 1a against 3 human cancer cell lines-A549 (lung), MCF7 (breast), and KB (oral); and a non-cancer cell line (NIH3T3) was determined by sulphorhodamine B based assay.     

Optical,thermal and mechanical characterization of Al(III)/Sb(III)-doped tris(thiourea)zinc(II) sulphate crystals

The influence of Al(III)/Sb(III)-doping on the properties of tris(thiourea)zinc(II) sulphate (ZTS) crystals grown by slow evaporation solution growth technique is reported. The as-grown crystals belong to orthorhombic system and cell parameters are, a = 7.77 Å, b = 11.13 Å, c = 15.47 Å, V = 1338 Å³ (Al(III)-doped) and a = 11.1996 Å, b = 7.770 Å, c = 15.5598 Å, V = 1368.3 Å³ (Sb(III)-doped). The structure and the crystallinity of the materials are further confirmed by powder X-ray diffraction analysis. The modes of vibrations of different functional groups present are identified by Fourier transform infrared studies. Thermogravimetric/differential thermal analysis studies reveal the purity of the materials and no decomposition is observed up to the melting point. Surface morphological changes due to doping are observed by scanning electron microscopy. Microhardness study was carried out to elucidate the mechanistic behavior microhardness studies were carried out to elucidate the mechanistic behavior. Second harmonic generation activity is much better in the case of Sb(III)-doping. The specimen is also characterized by dielectric studies.