Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• the inactive and toxic carboxylate form. A way to circumvent these drawbacks can be to conjugate the CPT to hydrophilic polymers and hereby creating a water-soluble polymeric CPT prodrug whereby the apparent aqueous solubility of the drug is increased. Furthermore, modification of the CPT hydroxy

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• in terms of water solubility and lack of aggregation. Keywords: cyclodextrins; PDT; protoporphyrin IX; prodrug; δ-aminolevulinic acid; Introduction Porphyrins have long been used as agents for tumor photodiagnosis (PDD) and photodynamic therapy (PDT) because of their preferential accumulation in

• ) cleavable ester bonds expected to release 1 by the action of intracellular enzymes. Taken together, the strategy would combine prodrug photosensitizer capability with molecular/drug transport in a single versatile bimodal system. Results and Discussion Synthesis: The suitable β-CD derivative to be linked

• . MCF7 cells were incubated with the colorless conjugate solution for 4 h, to allow conversion of prodrug 1 into PpIX [5][18]. Indeed, upon confocal microscopy imaging of the treated cells (λex = 568 nm), intense red fluorescence was observed (Figure 2), demonstrating that either (i) cell internalization

Synthesis of isoprenoid bisphosphonate ethers through C–P bond formations: Potential inhibitors of geranylgeranyl diphosphate synthase

• Xiang Zhou,
• Jacqueline E. Reilly,
• Kathleen A. Loerch,
• Raymond J. Hohl and
• David F. Wiemer

Beilstein J. Org. Chem. 2014, 10, 1645–1650, doi:10.3762/bjoc.10.171

• geranylgeranylated through posttranslational processing, instead is only partially modified [5]. Preparation of a prodrug form of DGBP does increase the impact of the drug by nearly an order of magnitude [7], but masking the negative charges of DGBP is not essential for observation of cellular activity. Following

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• prodrug candidates. The nucleoside reverse transcriptase inhibitors abacavir and lamivudine have been converted to the corresponding thiol-ending ester derivatives and then conjugated to ~3 nm glucose-coated gold nanoparticles by means of “thiol-for-thiol” ligand place exchange reactions. The drugs

• addition glucose-coated gold nanoparticles did not elicit any immune response in animal models [27][28]. We thus decided to use them as a scaffold to insert antiretroviral drugs to construct new multivalent anti-HIV systems. Here we describe the preparation of anti-HIV prodrug candidates and their assembly

• and lamivudine ester derivatives tailored onto the gold gluconanoparticles have an antiviral activity similar to the free drugs. Results and Discussion Preparation of anti-HIV prodrug-GNPs As a proof-of-principle for a further exploration of gold glyconanoparticles as drug-delivery system, we prepared

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• shown for hydroquinone in Scheme 24 [76]. O,O-dialkyl thiophosphite was also engaged in AT reactions to produce dinucleotide designed as an anti-HIV prodrug [77]. H-phosphonothioates are intermediates considered for the synthesis of nucleotide analogues. This functional group can be used as a

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• liberation of riluzole from the prodrugs was evaluated in plasma. One compound, an O-benzylserine derivative of riluzole (Figure 2, 1b), was identified as a candidate prodrug appropriate for in vivo testing, due to its stability in in vitro intestinal and microsomal assays and its ability to withstand

• metabolism by CYP1A2 [11]. Further development of this prodrug may allow for consistent riluzole plasma levels and thus more efficacious treatment among ALS patients. The modest success of riluzole in ALS treatment and the role of glutamate excitotoxicity in numerous disease states have motivated further

Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors

• Matthias G. J. Baud,
• Thomas Leiser,
• Vanessa Petrucci,
• Mekala Gunaratnam,
• Stephen Neidle,
• Franz-Josef Meyer-Almes and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2013, 9, 81–88, doi:10.3762/bjoc.9.11

• . Keywords: epigenetics; histone deacetylase; natural product; prodrug; psammaplin A; thioester; Introduction Chromatin is a macromolecular complex consisting of DNA, histone and nonhistone proteins. The epigenetic control of chromatin organization plays a major role in the regulation of gene expression

• unambiguously demonstrated that, similarly to the natural product and clinically approved romidepsin, psammaplin A is a prodrug, requiring reduction of its disulfide functionality to the corresponding thiol monomer 4 (X = OH), in order to potently inhibit HDACs (Scheme 1, right). The resulting thiol moiety acts

• parental psammaplin A (3), X = OH) is one strategy to “protect” the free thiol and allow for its effective dosing into cells, this prodrug strategy is reliant on intracellular reduction of the disulfide to the active thiol form. As such, cellular potency would be expected to correlate significantly with

Microwave- assisted ring closure reactions: Synthesis of 8-substituted xanthine derivatives and related pyrimido- and diazepinopurinediones

• Joachim C. Burbiel,
• Jörg Hockemeyer and
• Christa E. Müller

Beilstein J. Org. Chem. 2006, 2, No. 20, doi:10.1186/1860-5397-2-20

• position has led to A2A-selective antagonists, e.g. istradefylline (KW-6002, 1) [2], MSX-2 (2), and its water-soluble phosphate prodrug MSX-3 (3) (Figure 1) [3], which are interesting drug candidates, e.g. for the therapy of Parkinsons disease [4]. In contrast, bulky cycloalkyl residues such as cyclopentyl