@article {2542, title = {Paclitaxel incorporated in hydrophobically derivatized hyperbranched polyglycerols for intravesical bladder cancer therapy}, journal = {Bju International}, volume = {103}, number = {7}, year = {2009}, note = {ISI Document Delivery No.: 417GSTimes Cited: 6Cited Reference Count: 37Mugabe, Clement Hadaschik, Boris A. Kainthan, Rajesh K. Brooks, Donald E. So, Alan I. Gleave, Martin E. Burt, Helen M.}, month = {Apr}, pages = {978-986}, type = {Article}, abstract = {To develop paclitaxel incorporated into unimolecular micelles based on hydrophobically derivatized hyperbranched polyglycerols (dHPGs) for use as mucoadhesive intravesical agents against non-muscle-invasive bladder cancer. Two different types of dHPGs (HPG- C10-polyethylene glycol (PEG) and polyethyleneimine (PEI)-C18-HPG) were synthesized and paclitaxel was loaded into these using a solvent evaporation method. After physicochemical characterization of the resulting nanoparticles, four human bladder cancer cell lines were incubated with various concentrations of paclitaxel incorporated in dHPGs and the results were compared with those of paclitaxel formulated in Cremophor-EL (Taxol (R), Bristol-Myers-Squibb). In vivo, nude mice with orthotopic KU7-luc tumours were intravesically instilled with phosphate buffered saline, Taxol, or paclitaxel/HPG-C10-PEG. dHPGs are mucoadhesive nanoparticles with hydrodynamic radii of < 10 nm and incorporation of paclitaxel did not affect their size. The release profiles of paclitaxel from dHPGs were characterized by a rapid-release phase followed by a slower sustained-release phase. While the PEI-C18-HPG formulation released only approximate to 40\% of the initially incorporated paclitaxel, up to 80\% was released from HPG-C10-PEG. Moreover, only paclitaxel/HPG-C10-PEG was stable in acidic urine. In vitro, all paclitaxel formulations potently decreased bladder cancer proliferation although paclitaxel/HPG-C10-PEG was slightly less cytotoxic than standard Taxol. By contrast, in vivo, the mucoadhesive HPG-C10-PEG formulation of paclitaxel was significantly more effective in reducing orthotopic tumour growth than Taxol and was well tolerated. Intravesical administration of mucoadhesive nanoparticulate formulations of paclitaxel might be a promising approach for instillation therapy of patients with non-muscle-invasive bladder cancer.}, keywords = {ARCHITECTURES, bladder cancer, chemotherapy, DESIGN, DRUG-DELIVERY, hyperbranched polyglycerols, intravesical therapy, MANAGEMENT, MICROSPHERES, MUCOADHESION, orthotopic mouse model, PACLITAXEL, pharmacokinetics, POLYMERS, unimolecular micelles}, isbn = {1464-4096}, url = {://000264065100022}, author = {Mugabe, C. and Hadaschik, B. A. and Kainthan, R. K. and Brooks, D. E. and So, A. I. and Gleave, M. E. and Burt, H. M.} } @article {2549, title = {Synthetic Approaches to the Microtubule-Stabilizing Sponge Alkaloid Ceratamine A and Desbromo Analogues}, journal = {Journal of Organic Chemistry}, volume = {74}, number = {3}, year = {2009}, note = {ISI Document Delivery No.: 402HHTimes Cited: 6Cited Reference Count: 58Nodwell, Matt Pereira, Alban Riffell, Jenna L. Zimmerman, Carla Patrick, Brian O. Roberge, Michel Andersen, Raymond J.}, month = {Feb}, pages = {995-1006}, type = {Article}, abstract = {Two synthetic approaches to the microtubule-stabilizing ceratamine alkaloids are described. The first approach involved attempts to graft an aminoimidazole moiety onto an azepine ring to form partially hydrogenated versions of the unprecedented aromatic imidazo[4,5-d]azepine core of the ceratamines. This route ultimately failed because it was not possible to aromatize the partially hydrogenated ceratamine intermediates. A second approach started with tribromoimidazole that was sequentially metalated and functionalized to efficiently generate a key imidazole intermediate containing vinyl bromide and amide functionalities. An intramolecular Buchwald vinyl amidation reaction converted this key intermediate into a bicyclic imidazol[4,5-d]azepine that was at the same oxidation state as the aromatic core of the ceratamines. The 2-amino functionality present on the imidazole ring of the ceratamines was installed using a Buchwald/Hartwig amination reaction on a 2-chloroimidazole precursor. Deprotection and aromatization resulted in the first synthesis of desbromoceratamine A (55) and desmethyldesbromoceratamine A (60). An unanticipated addition of atmospheric oxygen was encountered during deprotection of the imidazole ring in the last step of the synthesis leading to C-11 oxygenated ceratamine analogues as byproducts. Evaluation of the synthetic ceratamines in a TG3 cell-based assay for mitotic arrest revealed that the C-14 and C-16 bromine substituents in ceratamine A (1) play a major role in the antimitotic potency of the natural product. The synthetic route to ceratamine analogues has provided sufficient quantities of desbromoceratamine A (55) for testing in mouse models of cancer.}, keywords = {6-PI-2-AZATRIENE ELECTROCYCLIZATION, AGELADINE-A, ANTIMITOTIC AGENTS, ARYL CHLORIDES, DIRECTED LITHIATION, HALIDES, IMIDAZOLE, PACLITAXEL, PALLADIUM-CATALYZED AMINATION, TAXOL}, isbn = {0022-3263}, url = {://000263004300005}, author = {Nodwell, M. and Pereira, A. and Riffell, J. L. and Zimmerman, C. and Patrick, B. O. and Roberge, M. and Andersen, R. J.} } @article {1032, title = {Boneratamides A-C, new sesquiterpenoids isolated from the marine sponge Axinyssa aplysinoides}, journal = {Journal of Natural Products}, volume = {67}, number = {10}, year = {2004}, note = {ISI Document Delivery No.: 865MRTimes Cited: 4Cited Reference Count: 14}, month = {Oct}, pages = {1752-1754}, type = {Article}, abstract = {Three new sesquiterpenoids, boneratamides A (1)-C (3), have been isolated as their methyl esters 4-6 from extracts of the marine sponge Axinyssa aplysinoides collected in Indonesia. The structures of methyl esters 4-6 were elucidated by analysis of spectroscopic data and confirmed by single-crystal X-ray diffraction analysis of 4.}, keywords = {AGENT, ANALOGS, BINDING, HEMIASTERLIN, NATURAL-PRODUCTS, PACLITAXEL, TUBULIN}, isbn = {0163-3864}, url = {://000224707700025}, author = {Williams, D. E. and Patrick, B. O. and Tahir, A. and Van Soest, R. and Roberge, M. and Andersen, R. J.} } @article {769, title = {Spirastrellolide A, an antimitotic macrolide isolated from the Caribbean Marine Sponge Spirastrella Coccinea}, journal = {Journal of the American Chemical Society}, volume = {125}, number = {18}, year = {2003}, note = {ISI Document Delivery No.: 675FLTimes Cited: 52Cited Reference Count: 14}, month = {May}, pages = {5296-5297}, type = {Article}, keywords = {AGENTS, PACLITAXEL, PEPTIDES, TUBULIN}, isbn = {0002-7863}, url = {://000182682700025}, author = {Williams, D. E. and Roberge, M. and Van Soest, R. and Andersen, R. J.} } @article {5025, title = {Antimitotic diterpenoids from Erythropodium caribaeorum: isolation artifacts and putative biosynthetic intermediates}, journal = {Tetrahedron Letters}, volume = {42}, number = {16}, year = {2001}, note = {ISI Document Delivery No.: 421EJTimes Cited: 18Cited Reference Count: 6}, month = {Apr}, pages = {2953-2956}, type = {Article}, abstract = {Two new natural products, caribaeorane (12) and 15-hydroxycaribaeorane (11), have been identified in Erythropodium caribaeorum extracts by isolation of their C-4 methylketals 10 and 9. It has been demonstrated that eleutherobin (1) is an isolation artifact. A proposal for the late stages of the biosynthetic pathway to the E. calibaeorum antimitotic diterpenoids is presented. (C) 2001 Published by Elsevier Science Ltd.}, keywords = {ELEUTHEROBIN, PACLITAXEL, SARCODICTYIN-A}, isbn = {0040-4039}, url = {://000168048900007}, author = {Britton, R. and Roberge, M. and Berisch, H. and Andersen, R. J.} } @article {5024, title = {Synthetic transformations of eleutherobin reveal new features of its microtubule-stabilizing pharmacophore}, journal = {Journal of the American Chemical Society}, volume = {123}, number = {35}, year = {2001}, note = {ISI Document Delivery No.: 467XNTimes Cited: 21Cited Reference Count: 13}, month = {Sep}, pages = {8632-8633}, type = {Article}, keywords = {AGENTS, COMMON PHARMACOPHORE, PACLITAXEL, TAXOL, TUBULIN}, isbn = {0002-7863}, url = {://000170729200037}, author = {Britton, R. and De Silva, E. D. and Bigg, C. M. and McHardy, L. M. and Roberge, M. and Andersen, R. J.} } @article {4774, title = {Solid-state and solution conformations of eleutherobin obtained from X-ray diffraction analysis and solution NOE data}, journal = {Tetrahedron Letters}, volume = {41}, number = {16}, year = {2000}, note = {ISI Document Delivery No.: 307YFTimes Cited: 2Cited Reference Count: 13}, month = {Apr}, pages = {2811-2815}, type = {Article}, abstract = {Single crystal X-ray diffraction analysis has revealed the solid-state conformation of the microtubule-stabilizing diterpenoid eleutherobin (1). NOE data obtained for 1 in CDCl3 and DMSO-d(6) are consistent with solution conformations that are virtually identical to the solid state conformation. (C) 2000 Elsevier Science Ltd. All rights reserved.}, keywords = {MICROTUBULE-STABILIZING AGENTS, PACLITAXEL, TAXOL}, isbn = {0040-4039}, url = {://000086681200012}, author = {Cinel, B. and Patrick, B. O. and Roberge, M. and Andersen, R. J.} }