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

• pharmacokinetic properties of the guest molecule, such as water solubility, bioavailability and stability [6][7]. In particular, many important drugs in cancer treatment are often toxic and/or sparingly soluble or even insoluble in water. Among other methods, reversible derivatization of these drugs into CD

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• resulting in a low oral bioavailability. This limitation can be overcome by using micro or nano-encapsulation methods that allow preparing fisetin oral liquid formulations that are well absorbed. Previously reported encapsulation strategies include liposomes [18], nanoemulsions [19], nanocochleates (which

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• bioavailability for many drugs and pharmacological tools. So, the preparation of fluorinated molecules is a very attractive research area for organic and medicinal chemists [17][18][19][20]. Our research program aims to synthesize new fluorinated molecules based on the easy access and the versatility of

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• to improve their in vivo bioavailability and stability. This progresses empowered the potential of therapeutic peptides, suggesting a production surge in the future. Besides this high potential, actual peptide production techniques suffer from major environmental issues [4][5][6]. Indeed, large

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• the enhancement of solubility, bioavailability and stability of drugs [2][3][4][5]. Moreover, being oligomers of α-D-glucopyranose, CDs possess an intrinsic chirality, thus they form diastereomeric inclusion complexes with enantiomeric pairs and frequently they exhibit enantioselectivity in aqueous

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

• encapsulation of construct 6 into the liposomes improved the drug distribution in cancer cells and was followed by cell death. This new liposomal trilobolide derivative not only retains the biological properties of pure trilobolide, but also enhances the bioavailability, and thus has potential for the use in

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• of antivirals due to their stability in biological fluids and their bioavailability. Some years ago, we described an approach leading to the C-ribosylated analogue 1 of ribavirin (Figure 2) with the key-steps of the synthesis being an indium-mediated alkynylation of a ribose derivative followed by

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• property can be utilized to protect the guest molecules from oxidation and degradation, to enhance their solubility and bioavailability, or to use the CD host as a drug carrier [1]. The potential application of these macrocyclic sugars in such pharmaceutical formulations required the understanding of the

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• research into their bioavailability being conducted, but also into manufacturing techniques that could be utilised for their production. Currently, research into non-solvent based synthetic methods is being pursued to eliminate the influence that the solvent has over the cocrystal formed. Cocrystal

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• , and bioavailability of drugs. CDs improve the above properties of drugs through complex formation, when formulated as injectable solutions, sprays, eye drops, powders, and tablets [7][8]. In recent years, the efficacy of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in the treatment of the NPC disease has

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• consumer market. It acts as a “virtual shortcut” in the drug discovery pipeline. CADD tools identify lead drug molecules for testing, can predict effectiveness and possible side effects, and assist in improving bioavailability of possible drug molecules. For example, in a recent study of CADD it was found

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy Department of Chemistry, Università della Calabria, Cubo 12C, 87036-Arcavacata di Rende (CS), Italy 10.3762/bjoc.12.214 Abstract Background: The peracetylation is a simple chemical modification that can be used to enhance the bioavailability

• derivatives of natural products demonstrated that peracetylation increases the cell intake, the intragastric absorbance and the oral bioavailability in respect to the unprotected natural compound [2][3][8][9]. It has been hypothesized that peracetylated molecules can exploit the same pathway than unprotected

• acetylated forms (Figure 3), among them the di-O-acetylated quercetin 13a was the major product (60% of the total reaction products, entry 13, Table 2). As the permeability and/or bioavailability of polyols is increased, no matter if the molecules are fully or partially acetylated, we decided to identify the

Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins

• Guozheng Huang,
• Simon Schramm,
• Jörg Heilmann,
• David Biedermann,
• Vladimír Křen and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 662–669, doi:10.3762/bjoc.12.66

• silymarin complex for protection of liver damage, and for preventing skin tumor promotion, these compounds have attracted efforts on their total synthesis (e.g., isosilybin) [6] and structural modification [5][7][8][9] to improve their water-solubility, bioavailability and biological activities. Recently

Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• biological activity is connected with a prohibited cellular uptake. Despite our model cannot tell anything about the bioavailability, metabolic half-life or side effects, due to our computations, compound 1 would have a lower affinity than linezolid even if it arrives at the ribosomal target. Though 1

Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

• Waratchada Sangpheak,
• Jintawee Kicuntod,
• Roswitha Schuster,
• Thanyada Rungrotmongkol,
• Peter Wolschann,
• Nawee Kungwan,
• Helmut Viernstein,
• Monika Mueller and
• Piamsook Pongsawasdi

Beilstein J. Org. Chem. 2015, 11, 2763–2773, doi:10.3762/bjoc.11.297

• pharmaceutical, medicine, cosmetics, food and agriculture [29]. β-CD and its derivatives have been widely used to increase the water solubility, stability, and consequent bioavailability of poorly water soluble drugs [30][31][32], such as β-CD in complex with piroxicam [33] and etodolac [34] and DM-β-CD in

• to increase water solubility, stability and bioavailability of those drugs [56][57]. In such a way, the bioavailability of genistein was found to be increased by complexation with CDs [58]. Cytotoxicity to cancer cell lines The cytotoxicity of flavanones and their inclusion complexes against three

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• endogenous metabolite of the most common estrogen hormone, 17β-estradiol, has been intensively studied owing to its proven potent antiangiogenic, antiproliferative and antitumoral activities [2][3]. However, its poor bioavailability has retarded its development as a drug [4][5]. Although recent reports of

• bioavailability. We therefore embarked on a study of 2ME [11] with the objectives of investigating both the interactions between CD molecules and 2ME in the solid-state as well as the effects of CDs on the aqueous solubility of 2ME, neither of these aspects having been given significant attention in the

• literature. Encapsulation of poorly soluble drug molecules by CDs with the aim of enhancing drug bioavailability has been practised for over four decades, the first demonstration of both in vivo and in vitro effects of complexation on drug release having been reported in the early 1970s [12][13]. Steroid

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

• Hang Ren,
• Haoyun An,
• Paul J. Hatala,
• William C. Stevens Jr,
• Jingchao Tao and
• Baicheng He

Beilstein J. Org. Chem. 2015, 11, 2509–2520, doi:10.3762/bjoc.11.272

• it imparts improve the bioavailability of fluorine-containing drugs. Relative to the unfluorinated derivative, fluorinated drugs have demonstrated favorable pharmacological, physicochemical, pharmacokinetic, pharmacodynamic and safety profiles for a number of compounds [21][22][23]. Several

Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

• Chompoonut Rungnim,
• Sarunya Phunpee,
• Manaschai Kunaseth,
• Supawadee Namuangruk,
• Kanin Rungsardthong,
• Thanyada Rungrotmongkol and
• Uracha Ruktanonchai

Beilstein J. Org. Chem. 2015, 11, 2306–2317, doi:10.3762/bjoc.11.251

• 10330, Thailand 10.3762/bjoc.11.251 Abstract Cyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents

• improve their bioavailability is challenging, and a requirement for the design and development of effective formulations. There are several ways to favorably enhance the solubility of poorly soluble drugs which include micronization, chemical modification, pH adjustment, complexation [1], co-solvent

• , dissolution rate, bioavailability, and stability (in comparison to the free drug), with controlled release also being possible [13][14][15][16]. In addition, co-solvent addition is a well-established method for increasing the equilibrium solubility of non-polar drugs. Recent studies combining co-solvent

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• cholesterol sequestration is found to be a crucial factor in developing NPC disease. Cyclodextrins (CyDs) are non-reducing cyclic glucose oligosaccharides obtained by enzymatic means from starch-containing raw materials and have been used for the enhancement of drugs solubility, stability and bioavailability

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• bioavailability of anticancer drugs. Thus, SuberAniloHydroxamic acid–cholesterol conjugates (SAHA–cholesterol) [11], cholesterol-based charged liposomes encaging doxorubicin [12] or curcumin [13] showed higher activity compared with the native drugs. Synthetic coumarin-caged cholesterol derivatives, for instance

Antioxidant potential of curcumin-related compounds studied by chemiluminescence kinetics, chain-breaking efficiencies, scavenging activity (ORAC) and DFT calculations

• Adriana K. Slavova-Kazakova,
• Silvia E. Angelova,
• Timur L. Veprintsev,
• Petko Denev,
• Davide Fabbri,
• Maria Antonietta Dettori,
• Maria Kratchanova,
• Vladimir V. Naumov,
• Aleksei V. Trofimov,
• Rostislav F. Vasil’ev,
• Giovanna Delogu and
• Vessela D. Kancheva

Beilstein J. Org. Chem. 2015, 11, 1398–1411, doi:10.3762/bjoc.11.151

• scavenging properties of the pertinent antioxidant reactants. The clinical use of curcumin is limited because of its low bioavailability, due to the hydrophobic nature of the molecule [8]. Schneider et al. [9] discussed the degradation and metabolism of curcumin, through products and their mechanism of

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• stable gradients of growth factors to regulate their bioavailability [11]. This matrix-immobilization of the factors might result in long-term binding to cell surface receptors, since the binding affinity of ECM-factors is relatively weak compared to growth factor receptor interactions [8]. Moreover, the

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• , and reduction of VEGFA and MMP9 expression. Despite its promising pharmacological properties, curcumin suffers from low in vivo bioavailability as a consequence of its low aqueous solubility, poor chemical stability and low absorption. Therefore, many analogs (Figure 2) were synthesized in order to

• complex partner, β-catenin [41]. Unfortunately, resveratrol has a dual effect on cells, depending on the situation and cell type – it can either induce or suppress angiogenic effects [42]. The low oral bioavailability and metabolic stability of resveratrol also limits its application [43]. Therefore, in

• an attempt to increase its bioavailability and stability, the structure of resveratrol was modified by methylation of the phenol groups [44] and by introduction of other groups on the phenyl ring (compounds 9–15, Figure 4) [45]. trans-3,4,4’,5-Tetramethoxystilbene (DMU-212) has improved

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• 10.3762/bjoc.11.22 Abstract Background: The aim of this study was to design and evaluate hybrid cyclodextrin (CD) nanocapsules intended for the oral delivery of the anticancer agent camptothecin (CPT) in order to maintain drug stability in the body and to improve its eventual bioavailability. For this

• higher when incorporated in hybrid CD nanocapsules compared with a DMSO solution. Conclusion: Oral CD nanocapsules indicating increased oral bioavailability might be a promising strategy to maintain the physiological stability and to improve the oral bioavailability of problematic anticancer drugs such

• occurs via the intravenous route [6][7]. However most anticancer drugs are not good candidates for oral delivery owing to their low absorption in the gastrointestinal tract (GI) and as a result exhibit low oral bioavailability [8][9]. In order to develop an effective oral chemotherapy, the

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• ]. Based on the notion that the 4-fluoro substituent of 11 might also enhance the hapten’s bioavailability, which would be advantageous in long-term treatments, we decided to determine briefly its hydrolytic resistance by subjecting both the partially deprotected glycosyl amino acid 12 and its native

• bioavailability of synthetic antigens and vaccines without affecting the induced antibody response and selectivity. Degradation of 4’F-TF antigen derivative 12 and its natural (synthetic) congener 13 by β-galactosidase from bovine testes. The amounts of intact disaccharide and the evolving degradation product 15