@article { ISI:000257424800017, title = {Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of alpha-glucosidase}, journal = {Organic \& Biomolecular Chemistry}, volume = {6}, number = {14}, year = {2008}, month = {JAN}, pages = {2587-2595}, publisher = {ROYAL SOC CHEMISTRY}, type = {Article}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from D-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of a-glucosidase with K(i) values ranging as low as 1.07 mu M, 16.4 mu M, and 88.2 mu M, respectively. Replacement of the hydroxy methylene moiety of 19 (K(i) 33\% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 mu M) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of 33 by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 mu M to K(i) 72.3 mu M).

}, issn = {1477-0520}, doi = {10.1039/b804278k}, author = {Pandey, Ganesh and Bharadwaj, Kishor Chandra and Khan, Mohammad Islam and Shashidhara, K. S. and Puranik, Vedavati G.} } @article { ISI:000272134300006, title = {Interaction of alpha-mannosidase from aspergillus fischeri with glycosidase inhibitors, metal ions and group specific reagents}, journal = {Research Journal of Biotechnology}, volume = {4}, number = {4}, year = {2009}, month = {NOV}, pages = {39-48}, publisher = {RESEARCH JOURNAL BIOTECHNOLOGY}, address = {SECTOR A-80, SCHEME NO 54, VIJAY NAGAR, A B ROAD, INDORE, 452 010 MP, INDIA}, abstract = {

As an initial step towards using alpha-mannosidase as a target against anticancer drugs, inhibition studies of a model enzyme, class II alpha-mannosidase from Aspergillus fischeri in presence of polyhydroxy piperidine derived glycosidase inhibitors, metal ions and amino acid specific reagents were carried out to reveal the sensitivity of the enzyme. Three of the derivatives (Compound 20, 32 and 39)(11) showed competitive inhibition (K(i) =45, 48 and 235 mu M) and the binding of the inhibitors to the enzyme was entropically driven. Among the metal ions checked, Cu(++) (K(i) = 21nm) and Se(++) ions (K(i) = 32 mu M) showed noncompetitive and Co(++) (K(i) = 1.195 mM) showed competitive inhibition of the enzyme activity with insignificant change in the secondary structure of the protein. The above studies exhibit the Potential of the enzyme in studying anticancer drugs. Treatment of the enzyme with group specific reagents showed the presence of carboxylate, Arg and Cys at the active site. Substrate protection studies and kinetics of the modified enzyme confirmed the above results. Trp and His at the active site were observed to be in proximity.

}, keywords = {active-site, alpha-Mannosidase, Chemical modification, Glycosidase inhibitors, metal ions}, issn = {0973-6263}, author = {Shashidhara, K. S. and Gaikwad, S. M. and Khan, Mohammad Islam and Bharadwaj, Kishor Chandra and Pandey, G.} } @article { ISI:000341360400024, title = {Divergent total synthesis of 1,6,8a-tri-epi-castanospermine and 1-deoxy-6,8a-di-epi-castanospermine from substituted azetidin-2-one (beta-lactam), involving a cascade sequence of reactions as a key step}, journal = {Organic \& Biomolecular Chemistry}, volume = {12}, number = {37}, year = {2014}, month = {JUL}, pages = {7389-7396}, publisher = {ROYAL SOC CHEMISTRY}, type = {Article}, address = {THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND}, abstract = {

A divergent, short, and novel total synthesis of 1,6,8a-tri-epi-castanospermine (7) and 1-deoxy-6,8a-di-epi-castanospermine (8) has been developed via a common precursor, 15, obtained from D-mannitol derived beta-lactam. The key step involves a one pot cascade sequence of trimethyl sulfoxonium ylide based cyclization of epoxy sulfonamide 14 via epoxide ring opening, one carbon homologation followed by intramolecular cyclization.

}, issn = {1477-0520}, doi = {10.1039/c4ob00948g}, author = {Tiwari, Dipak Kumar and Bharadwaj, Kishor Chandra and Puranik, Vedavati G. and Tiwari, Dharmendra Kumar} }