Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• its receptor [44][45][46], clustered RGD-containing compounds were developed and were shown to exhibit attractive biological properties for the imaging of tumors [47][48][49][50] and for the targeted drug delivery [51][52][53]. In the course of designing phototherapeutic agents that could specifically

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• , mainly as drug delivery systems [4][7][8][9][10][11][12], and their utilisation as organic materials have constantly been highlighted [13][14][15][16][17]. In the latter context, dendritic liquid crystals defines a well-established area in the organic materials domain [18], including few examples of s

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• ]. However, it exerted a significantly lower endocrine effect in mammals than the human GnRH (GnRH-I: Glp-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) and other GnRH analogues [9]. This low hormonal effect might provide an advantage in the treatment of hormone-independent tumors [10]. Targeted drug delivery is a

• clinical trial, which was discontinued for all indications under development in May 2017 [12]. GnRH-III-based conjugates have been investigated in our laboratory as promising candidates for targeted drug delivery with positive results in human tumor cell lines, both related (e.g., MCF-7) and unrelated (e.g

• ]. These side effects can limit the applicability of these chemotherapeutic drugs. The conjugation of doxorubicin and daunorubicin to a GnRH-III-based targeting peptide could lead to decreased cardiotoxic effect through the more specific drug targeting. Drug delivery systems containing doxorubicin

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• Jiyun Sun Xiaohua Zhen Huaibin Ge Guangtao Zhang Xuechan An Yunfei Du Tianjin Key Laboratory for Modern Drug Delivery and High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China Collaborative Innovation Center of Chemical Science and Engineering

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• upper and/or lower rims of the molecular skeleton, they have been widely used for construction of artificial host molecules and found applications in various fields like molecular recognition, sensing, self-assembly, catalysis, nanoscience, drug delivery and separation science [7][8][9][10][11][12][13

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• excluded. However, initial drug delivery studies demonstrated the high versatility of these new peptides as efficient transport vectors targeting specifically nuclei and nucleoli. In future, they could be further explored as parts of newly created peptide–drug conjugates. Keywords: anticancer drugs; cell

• aimed to investigate the effect of the fusion peptides on drug delivery and efficacy within co-administration. Indeed, the covalent binding of doxorubicin to different CPPs was already reported and the induction of cell death in various cell lines has been observed [39][40]. However, the non-covalent

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• ranging from drug delivery through to tissue engineering [3][4]. Collectively, the importance of the 2-oxazoline scaffold for translational research, together with its strategic value in the design of chiral ligands and auxiliaries [5][6][7], has culminated in a rich and innovative arsenal of synthetic

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• , including important PDCs that have progressed to phase III clinical trials. Last, we address possible difficulties that may emerge during the synthesis of PDCs, as also report ways to overcome them. Keywords: bioconjugates; cancer; drug delivery; PDC; peptide; peptide–drug conjugate; side-products in PDCs

• , drug delivery vehicles that can be tailored for different types of cancer and shape personalized therapeutics are continuously gathering attention. Such drug delivery systems are of ultimate importance to effectively surpass these hurdles and eventually improve drug potency. Charting the malignant

• main challenge of the drug delivery concept is to transport sufficient amount of the cytotoxic agent to a specific location with minimum adverse side effects. To conquer this, various approaches are being exploited at the moment. These include, but are not limited to: a) utilization of drug delivery

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• importance for regulating molecular properties like polarizability [1] and in various biochemical processes, including protein folding [2] and stability [3], replication of DNA and RNA [4], enzyme catalysis [5], proton relay mechanism [6], and drug delivery [7]. Energy decomposition analysis (EDA) schemes

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• release; NGR peptides; oxime-linkage; targeted drug delivery; Introduction Targeted chemotherapy is one of the most promising approaches for selective cancer treatment that may decrease the toxic side effects of anticancer drugs. This therapeutic approach is based on the fact that tumor specific

• receptors are highly expressed on cancer cells/tissues. NGR (Asn-Gly-Arg) motif-containing peptides identified by phage display are suitable candidates for selective drug delivery. NGR peptides bind to CD13-receptors on tumor cells and tumor related angiogenic blood vessels [1][2]. CD13 is a transmembrane

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• aggregation could be observed in HPLC or MS measurements, we assume that the presence of the β-hairpin structure is a feasible conception in these cases. Stability/degradation of the GnRH-III bioconjugates Drug delivery systems (DDS) are promising therapeutics for tumor therapy providing a selective

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• (X = I or Br) in water [100]. Other examples of water-soluble dendrimers are peptide- and glycol-based dendrimers [102][103]. As a result of their compositional versatility, they have been reported in many applications for biomedical engineering (e.g., glycopeptide dendrimers for drug delivery [104

• crystalline domains. The nanogels display excellent swelling behavior and are shape resistant [43][110]. Due to these unique properties they have mostly been studied as materials in biomedical applications such as controlled drug delivery [111]. Nanogels show promise as nanoreactors as they not only are

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• for the use of 2’-O-RSSM-modified RNAs as prodrugs of siRNAs. Modifications at the extremities Disulfide bonds are attractive in designing drug-delivery systems. Indeed, lipophilic moieties may be attached to ONs to enhance cellular uptake. In particular, a cleavable disulfide linker has been used at

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• , αVβ6, and α5β1. These data indicate that in this case the cyclo[DKP-isoDGR]-α-amanitin conjugates are possibly internalized by a process mediated by integrins different from αVβ3 (e.g., αVβ5). Keywords: antitumor agents; cancer; drug delivery; integrins; peptidomimetics; Introduction α-Amanitin is a

Synthesis of naturally-derived macromolecules through simplified electrochemically mediated ATRP

• Paweł Chmielarz,
• Tomasz Pacześniak,
• Katarzyna Rydel-Ciszek,
• Izabela Zaborniak,
• Paulina Biedka and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2017, 13, 2466–2472, doi:10.3762/bjoc.13.243

• naturally-derived macromolecules showed narrow MWDs (Đ = 1.08–1.11). 1H NMR spectral results confirm the formation of quercetin-based polymers. These new flavonoid-based polymer materials may find applications as antifouling coatings and drug delivery systems. Keywords: flavonoids; on-demand seATRP

• macromolecules [37][38][39], widely used as dental adhesives, controlled release devices, coatings, and in pharmaceutical industry [40][41]. Therefore, it is expected that these synthesized naturally-derived macromolecules can become key elements of antifouling coatings and drug delivery systems. ATRP is one of

• , and 1H NMR prove the successful preparation of the star-shaped polymers. These new polymer materials create potential possibilities of using them as key elements of biologically active thin films in tissue engineering and as drug delivery systems. 1H NMR analysis of QC-Br5 (Mn = 1,050, Ð = 1.11) after

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• ], luminescence [67], non-linear optics [68] and magnetism [69], as well as contrast agents for magnetic resonance imaging (MRI) [70] and as drug carriers in systems for controlled drug delivery and release [64][71][72][73][74][75][76][77][78][79][80]. Also under development are new systems with potential use in

• be studied for their potential medicinal applications. Here, the main focus was their use as drug-delivery systems [71][72][89], with particular attention to the toxicity of the metal centers [84]. Toxicity is a concern not only for the safe use of these compounds for humans but also for

• soaking methods. However, a significant number of these frameworks obtained by mechanochemistry with potential to be used as drug delivery systems have not yet been fully tested for the loading of drugs. Pichon et al. proposed the first BioMOF synthesized by mechanochemistry using copper acetate and

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• various sizes (4.7–8.3 Å) into which distinct compounds may enter and form inclusion complexes, an ability that is thoroughly used by the pharmaceutical industry for the formation of drug delivery systems [1][2][3][4][5]. The formation of an inclusion complex often results in a favorable change of

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• Beilstein Journal of Organic Chemistry also provides further insights into the synthesis and properties of CD superstructures, covering many aspects such as catalysis, molecular recognition, colloids, polyrotaxanes, drug delivery and more. Gerhard Wenz Saarbrücken, September 2017

New bio-nanocomposites based on iron oxides and polysaccharides applied to oxidation and alkylation reactions

• Daily Rodríguez-Padrón,
• Alina M. Balu,
• Antonio A. Romero and
• Rafael Luque

Beilstein J. Org. Chem. 2017, 13, 1982–1993, doi:10.3762/bjoc.13.194

• nanocomposites with diverse applications in catalysis, sensing, drug delivery and adsorption [25][26][27][28]. In addition, mechanochemical protocols have also been employed to functionalize the surfaces of magnetic nanoparticles (MNPs) with monosaccharides [29] and to obtain bio-nanocomposites based on proteins

β-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling aqueous networks designed for controlled complexation and release of small molecules

• Liang Yan,
• Duc-Truc Pham,
• Philip Clements,
• Stephen F. Lincoln,
• Jie Wang,
• Xuhong Guo and
• Christopher J. Easton

Beilstein J. Org. Chem. 2017, 13, 1879–1892, doi:10.3762/bjoc.13.183

• . Depending upon their composition, these networks and related systems retain drug and similar molecules to varying extents which renders them of interest as potential drug delivery systems [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47

• dependent upon the structure of the dye, and the structure of the network and its viscosity. Potentially, these systems form the basis for the development of controlled drug delivery systems for topical and wound applications, where the factors for drug release are likely to be similar to those controlling

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• reduces its potential medicinal applications. The targeted delivery of hydrophobic drugs can be achieved using liposome-based carriers. Therefore, we designed a traceable liposomal drug delivery system for trilobolide. The fluorescent green-emitting dye BODIPY, cholesterol and trilobolide were used to

• theranostic applications. Keywords: BODIPY conjugates; cancer targeting; drug delivery; liposomes; natural compounds; sesquiterpene lactone trilobolide; Introduction Targeted (smart) drug delivery is a method for specific delivering of an active compound preferentially to some cells or tissues in the human

• active construct 6 from the liposomes. Further tests are necessary to confirm this hypothesis. Conclusion In summary, in order to develop a drug delivery system for potential theranostic applications, we prepared a submicron liposome-based formulation of a cytotoxic agent, sesquiterpene lactone

One-pot synthesis of block-copolyrotaxanes through controlled rotaxa-polymerization

• Jessica Hilschmann,
• Gerhard Wenz and
• Gergely Kali

Beilstein J. Org. Chem. 2017, 13, 1310–1315, doi:10.3762/bjoc.13.127

• drug delivery or tissue engineering. (a) GPC trace of the polyHEMA-co-polyisoprene polyrotaxane 1 and (b) 500 MHz 1H NMR and DOSY spectra of poly(TRIS-AAm)-co-polyisoprene polyrotaxane 2 in DMSO-d6. (a) GPC traces of the macroCTA 5 (solid line) and the poly(TRIS-AAm)-b-polyisoprene-b-poly(TRIS-AAm

Correction: Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 1136–1138, doi:10.3762/bjoc.13.112

• original article. N/P-doped hollow CDs for efficient drug delivery of doxorubicin. Corrected Scheme 15 of the original article. N/P-doped green-emissive CDs working in tandem with hyaluronic acid-coated AuNPs to monitor hyaluronidase activity. Corrected Scheme 20 of the original article. Different

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• resulting biological processes [3][4]. The increasing ability to manipulate material at the nanosize allowed the development of many glyco nanoparticles helpful in a wide range of applications, from the drug delivery to the imaging [5][6][7]. Among the large number of nanomaterials, gold is one of the main

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• bilayers, they can be used to stabilize liposomes for drug delivery purposes. The applicability of this approach was already tested for a large variety of natural and artificial bolalipids [12][16][17][18][19][20][21][22]. The isolation of archaeal bolalipids from natural sources is expensive and often

• lamellar structure – prerequisites for the use as drug delivery vehicle – could not be observed, and bilayer fragments as well as elongated micelles were formed instead [35]. The isomers PC-C17mPhC17-PC and PC-C17oPhC17-PC, bearing a meta or ortho substitution at the central phenyl ring, showed the