Woodinine and its Stereomers - Absolute Configuration

The synthesis of all the four stereomers of the alkaloid woodinine ( 12a )¹⁾ is described and the stereochemical conclusions of Païs³⁾ and Still⁶⁾ are discussed. The absol. configurations of woodinine ( 12a ) and its diastereomer 8b are unequivocally deduced from the pertinent piperazinediones 16 and 17 .     

Synthese von Carbazolderivaten, 2. Mitt.: 2-Substituierte Indole als Zwischenprodukte von Pyrrolino[3,4-c]carbazolen

Synthesis of Carbazole Derivatives, II: C-2-substituted Indoles as Intermediates of Pyrrolino[3,4-c]carbazoles Starting from the indole derivatives 4, 7 and 15 Grignard reaction, nucleophilic substitution at the pertinent dithian, and Wittig reaction afford preparatively useful side chains. By intramolecular Michael reaction the pertinent compounds lead to the pyrrolidino- and pyrrolino[3,4-c]carbazoles 32 and 33 , respectively.     

Comparison of active and passive targeting of docetaxel for prostate cancer therapy by HPMA copolymer-RGDfK conjugates

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer-docetaxel-RGDfK conjugate was synthesized, characterized, and evaluated in vitro and in vivo in comparison with untargeted low and high molecular weight HPMA copolymer-docetaxel conjugates. The targeted conjugate was designed to have a hydrodynamic diameter below renal threshold to allow elimination post treatment. All conjugates demonstrated the ability to inhibit the growth of DU145 and PC3 human prostate cancer cells and the HUVEC at low nanomolar concentrations. The targeted conjugate showed active binding to α(v)β(3) integrins in both HUVEC and DU145 cells, whereas the untargeted conjugate demonstrated no evidence of specific binding. Efficacy at two concentrations (20 mg/kg and 40 mg/kg) was evaluated in nu/nu mice bearing DU145 tumor xenografts treated with a single dose of conjugates and compared with controls. RGDfK targeted and high molecular weight nontargeted conjugates exhibited the highest antitumor efficacy as evaluated by tumor regression. These results demonstrate that α(v)β(3) integrin targeted polymeric conjugates with improved water solubility, reduced toxicity and ease of elimination post treatment in vivo are promising candidates for prostate cancer therapy.     

Silk-elastinlike protein polymers for matrix-mediated cancer gene therapy

Silk-elastinlike protein polymers (SELPs) are recombinant polymers designed from silk fibroin and mammalian elastin amino acid repeats. These are versatile materials that have been examined as controlled release systems for intratumoral gene delivery. SELP hydrogels comprise monodisperse and tunable polymers that have the capability to control and localize the release and expression of plasmid DNA and viruses. This article reviews recent developments in the synthesis and characterization of SELP hydrogels and their use for matrix-mediated gene delivery.