Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB₂-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

• Yang Bai,
• Cai-ping Liu,
• Di Chen,
• Long-hai Zhuo,
• Huai-tian Bu and
• Wei Tian

Beilstein J. Org. Chem. 2019, 15, 1925–1932, doi:10.3762/bjoc.15.188

• -responsive supramolecular self-assemblies have been constructed, the controlled drug delivery induced by morphology transitions of these supramolecular self-assemblies on the basis of host–guest-conjugated monomers (HGCMs) are few reported. In this paper, the self-assembly behaviors of AB2-type HGCMs, e.g

• varied morphology could inhibit cancer cell proliferation, indicating their potential application in the field of drug delivery. Keywords: β-cyclodextrin; controlled drug delivery; host–guest interaction; stimuli-responsive; supramolecular self-assemblies; Introduction Supramolecular self-assemblies

• hydrophobic core and β-CD moieties as outer hydrophilic shell. The basic cell experiments confirmed that the pH-responsive supramolecular self-assemblies based on β-CD-BM2 have a potential application in the field of drug delivery. Results and Discussion Synthesis of the host–guest-conjugated amphiphilic

Novel macrocycles – and old ones doing new tricks

• Wei Jiang and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2019, 15, 1838–1839, doi:10.3762/bjoc.15.178

• diversified. They are not only tools for studying molecular recognition and molecular machines, but are also key components for sensing, supramolecular catalysis, (chiral) separation, drug delivery, or smart materials. Many new macrocycles have recently been reported, with pillararenes being one of the most

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• contribute to the recognition of the adjuvant compound by specific mannose receptors expressed at immune cells. Mannosylated drug delivery systems enhance uptake and activation of dendritic cells and increase T cell proliferation [24][27][28]. Mannosylation of the adamantylated desmuramyl peptides amplified

• most suitable position of adamantane in this class of compounds is at the peptide N-terminus. Adamantane can act as membrane anchor for mannose structures and thus be exposed on liposome surfaces and as such used in targeted drug delivery [37]. It can be also incorporated into a β-cyclodextrine cavity

• , a powerful supramolecular nanoparticle carrier for targeted drug delivery [38]. Previous research suggested a design of mannosylated desmuramyl peptides with adamantane at the C-terminus in order to facilitate the incorporation into the hydrophobic layer of the cavity because of the minor steric

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• . Galactose and fructose also allow tumor growth in the absence of glucose. Boronic acid derivatives have gained interest in the last years in different fields such as the development of enzyme inhibitors, drug delivery polymers, saccharide sensors and as boron carriers for BNCT, e.g., amino acid derivatives

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• ligands with novel features. They have found various applications in chemical [5], analytical [6][7][8][9], and engineering materials fields (self-assembling monolayers, surfactants, sensors [10][11]), in polymer synthesis [12][13], controlled drug-delivery systems [14], and so on, besides the biochemical

Fabrication, characterization and adsorption properties of cucurbit[7]uril-functionalized polycaprolactone electrospun nanofibrous membranes

• Changzhong Chen,
• Fengbo Liu,
• Xiongzhi Zhang,
• Zhiyong Zhao and
• Simin Liu

Beilstein J. Org. Chem. 2019, 15, 992–999, doi:10.3762/bjoc.15.97

• or some low-molecular weight organic compounds [1][2][3][4][5]. With the unique advantages of ultrafine diameter, high specific surface area, controllable morphology, and easy functionalization, electrospun nanofibers have potential applications in various areas including drug delivery and tissue

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• adjuvants, glycolipid–phospholipid drug delivery systems and for the formulation of GVs that can be used as tools to bind to various bacterial lectins depending on the mono- or disaccharides used. As a first and relevant conclusion, in silico and in vitro studies demonstrated that two of those compounds

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• Ayato Yamada Manabu Abe Yoshinobu Nishimura Shoji Ishizaka Masashi Namba Taku Nakashima Kiyofumi Shimoji Noboru Hattori Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan Hiroshima Research Centre for Photo-Drug

• -Delivery Systems (HiU-P-DDS), Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8526, Japan JST-CREST, K’s Gobancho 6F, 7, Gobancho, Chiyoda-ku, Tokyo 102-0075, Japan Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8571

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

• Antonella Di Vincenzo,
• Antonio Palumbo Piccionello,
• Alberto Spinella,
• Delia Chillura Martino,
• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• external stimuli is a highly desirable property for tailored materials designed to accomplish particular functions, such as targeted drug delivery systems, as accounted for by the present burst in literature reports [1][2][3][4][5][6]. In this context, we have been recently interested in the synthesis of

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• electronics, fuel cells, gene and drug delivery [8][9][15][38][39][40]. Compared with diblock and triblock copolymers, not to speak about polymer blends, multiblock copolymers often demonstrate superior mechanical properties, biocompatibility, biodegradability, compatibilizing ability, and tendency to form

• recognition, imaging, and drug delivery in aqueous media [4][5][6][67]. They have a low tendency to entangle and can rapidly self-assemble in selective solvents even at very low concentrations forming large-domain microstructures. The facile synthesis of norbornenyl-terminated di- and triblock poly

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• metathesis into natural metabolic pathways to allow synthesis of fine chemicals [14]. Also, a targeted reaction in a certain environment within a living cell with a precise release or activation of the catalyst would enable new ways of drug delivery. The challenge to overcome this regard is the deactivation

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• fields including adsorbent, optical devices, water purification, drug delivery, and catalysis. Silica nanoparticles with different structures have extensively investigated due to their simple preparation and diverse industrial applications. In addition, SiO2 nanoparticles with high surface area commonly

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• tag; Fmoc-Lys-(Tfa)-OH; prostate cancer and ovarian cancer; solid-phase peptide synthesis; Introduction The understanding of cell processes is indispensable to devise new strategies for diagnosis and treatment of cancer and inflammatory diseases through targeted drug delivery techniques [1]. The

• malignancy [23] and inflammatory diseases. They are also utilized for targeted drug delivery [24][25] of therapeutics to avoid any off-site toxicity to normal and healthy cells. Unfortunately, strategies to construct diagnostic and therapeutic chemical tools consisting of a polypeptidic spacer, a homing

• which express neither PSMA nor folate receptors [panels (iv) and (viii)]. The absence of any rhodamine B bioconjugates 13 and 17 uptake in the cytoplasm of negative cell line, PC-3 cells, show that the bioconjugates are very specific which is an important criterion in targeted drug delivery systems for

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• approaches to diminish this kind of cytotoxic effects on healthy tissues is the employment of drug delivery systems directed specifically to cancer cells. The chemotherapeutic drug targeting is often based on the receptors for certain peptide hormones that are preferentially expressed by cancer cells. The

• utilization of these receptors for cancer cell targeting allows for minimizing the toxic side effects and producing high drug concentration selectively at the tumor site. In general, drug delivery systems consist of a targeting moiety in order to recognize a receptor on tumor cells and a cytotoxic drug

• )]-GnRH-III(Dau=Aoa) was shown to be the best-internalized conjugate and this ability proved to be independent of the tumor cells. Antiproliferative/cytotoxic effect of conjugates One of the major requirements for a drug-delivery conjugate is the ability to provide the antitumor activity of the attached

Coordination-driven self-assembly of discrete Ru₆–Pt₆ prismatic cages

• Aderonke Ajibola Adeyemo and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2018, 14, 2242–2249, doi:10.3762/bjoc.14.199

• donors and transition metals as electron-deficient acceptors. Diverse functionalities embedded in these homometallic architectures have found useful applications in chemical sensing [24][25][26][27][28][29][30][31][32][33][34][35], catalysis [11][36][37][38][39][40][41][42][43][44][45][46], drug delivery

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• as bioimaging and self-assembled drug delivery systems [33][34][35][36][37][38][39][40]. For example, our group demonstrated a direct host–guest complexation-based drug delivery system for oxaliplatin by carboxylatopillar[6]arene [36]. The encapsulation could not only improve the drug‘s stability in

• guests exhibit a significant fluorescence intensity enhancement and the intensity is strong enough to be distinguished by the naked eye. The easy accessibility, good water-solubility and nice binding properties make 2,2’-CBP4 be applicable in the biomedical field, for example, chemical sensors, drug

• delivery, supramolecular amphiphiles, etc. Experimental 2,2’-OEtBP4 was synthesized according to our previously reported method [47]. P and B were purchased from Shanghai Aladdin Bio-Chem Technology Co.,LTD. 1H NMR and 13C NMR spectra were recorded on a Bruker AV500 instrument. The fluorescence emission

A self-assembled photoresponsive gel consisting of chiral nanofibers

• Lei Zou,
• Dan Han,
• Zhiyi Yuan,
• Dongdong Chang and
• Xiang Ma

Beilstein J. Org. Chem. 2018, 14, 1994–2001, doi:10.3762/bjoc.14.174

• other interactions. Interestingly, some of them can be assembled into distinctive nanostructures through gel formation [4][5][6]. Various functional nanostructures have shown great potential for applications in many important areas, for example, nanofabrication [5][7][8][9][10], drug delivery [11][12

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