First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• class of 4H-thiopyran derivatives. The presence of a quinone system is an important structural aspect of this class as it is common in many naturally occurring compounds, e.g., dyes such as alizarin, carminic acid, and isoprenoid dyes, as well as drugs such as doxorubicin. In addition, the presence of

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

• Chemistry, Pázmány P. stny 1/A, Hungarian Academy of Science, Budapest, 1117, Hungary 10.3762/bjoc.14.136 Abstract Background: Cardiomyopathy induced by the chemotherapeutic agents doxorubicin and daunorubicin is a major limiting factor for their application in cancer therapy. Chemotactic drug targeting

• -conjugates containing doxorubicin, daunorubicin and methotrexate were investigated in this study. Their cytotoxicity was determined on primary human cardiac myocytes (HCM) and human umbilical vein endothelial cells (HUVEC) using the xCELLigence SP system, which measures impedance changes caused by adhering

• cells on golden electrode arrays placed at the bottom of the wells. Slopes of impedance–time curves were calculated and for the quantitative determination of cytotoxicity, the difference to the control was analysed. Results: Doxorubicin and daunorubicin exhibited a cytotoxic effect on both cell types

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

• initial study for the delivery of the anticancer drug doxorubicin. Results and Discussion Peptide synthesis and analysis of the secondary structure We chose two different nuclear-targeting sequences, on the one hand the N50 peptide, which was derived from the NF-κB/p50 subunit. N50 binds the adaptor

• . Therefore, HeLa and MCF-7 cells were exposed to the chemotherapeutic drug doxorubicin (DOX) that is already clinically applied in cancer therapy [37]. Doxorubicin interacts with DNA by intercalation and thereby inhibits the macromolecular biosynthesis [38]. Instead of covalent conjugation of the drug, we

• 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

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

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

• drug to the tissues which usually occurs via the bloodstream. Conventional chemotherapeutic drugs (gemcitabine, paclitaxel, doxorubicin, etc.) are not capable to be selectively delivered to the tumor sites and they end up scattered in the whole body. 3) Metabolism is a standard biological strategy for

• anticancer drugs utilized to treat malignancies at the moment. Among this large pool of cytotoxic drugs, an array of them has been utilized as toxic warheads in PDCs and five representative examples are gemcitabine, doxorubicin, daunorubicin, paclitaxel and camptothecin (Figure 4). The main drawback of these

• therapeutic window of the parent cytotoxic agent. Since different drugs may employ a different mechanistic approach to kill cells, the appropriate drug is selected according to features characterizing the targeted cancerous cells. For instance, daunorubicin and doxorubicin possess similar mechanisms of action

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

• , 9Pro-EA] and triporelin [6D-Trp], which are used as pharmaceutical peptides to treat inter alia hormone dependent prostate and/or breast cancer [7]. Since the mid-1980s cytotoxic GnRH-I derivatives were developed and investigated to treat tumor cells [4][5][8][9]. Anthracyclines such as doxorubicin

• preclinical and clinical studies, was zoptarelin-doxorubicin also known as AEZS-108 (previously AN-152) [16]. The anthracycline doxorubicin was conjugated to the ε-amino group of GnRH-I-[6D-Lys] by insertion of a glutaric acid linker. The resulting ester bond can be cleaved by carboxylesterases, leading to

• superagonist triptorelin [14]. In addition, the internalization and the intracellular localization of AN-152 were visualized by CLSM [14]. Despite all these promising findings, zoptarelin-doxorubicin did not achieve its primary endpoint in phase 3 clinical studies on endometrial cancer [18]. A natural isoform

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

• promising candidate to biomedical applications [8]. Indeed, ZIF-8 has been largely used to encapsulate APIs such as doxorubicin, an anticancer drug [96][142] or even as an efficient pH-sensitive drug-delivery system [92][95][143][144]. Usually, the encapsulation of small molecules into MOFs involves two

• , including doxorubicin [142]. The controlled drug release is due to the small pore size of ZIF-8 that prevents premature release and its pH sensitivity. At pH 5–6 there dissociation of the framework takes place with consequent drug release ideal to target cancer cells [95]. Mechanochemistry in the synthesis

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• antineoplastic doxorubicin and by the antiparasitic avermectin (Figure 1a) [1]. PK are assembled from acyl-coenzyme A (acyl-CoA) units via a series of Claisen-type condensation reactions catalyzed by polyketide synthases (PKS) (Figure 1b). PKS occur as large multifunctional enzymes, termed megasynthases, which

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

• structures in Schemes 9, 15, 20, and 22. The corrected schemes are shown in this Correction. The wrong configuration was depicted for C-4 (carrying the OH group) in the pyranose ring of doxorubicin in Scheme 9; the corrected scheme (Scheme 1) is shown below: The NH group was missing at C-2 of the GlcNAc

• 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

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• (MCF-7) was also evaluated, using MTT assay [23] with doxorubicin as a positive control. As shown in Table 3, the isolates showed a similar activity profile with that of the antifungal activity, e.g., only 5 and 6 were active and others were inactive (>50 μM) toward all the tested cell lines. These

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

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• synthesised CDs. The material’s unique properties deemed them ideal candidates for drug-delivery purposes. The team chose doxorubicin (DOX) as the model drug for this purpose and loading of DOX onto the CD was demonstrated via a change in the ZP from −9.3 mV to −0.13 mV, suggesting that an electrostatic

• negatively-charged polysaccharide, and shown by AFM, DLS and TEM, to have formed nano-aggregates of up to 250 nm. Interestingly, the emissive properties of the CDs were unchanged upon complexation to HA. The resultant nano-aggregates were then loaded with doxorubicin (DOX) and a strong correlation between

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

• nitric oxide under illumination with visible light, resulting in amplified cancer-cell mortality [9]. By attaching porphyrin to γ-CD and dimeric β-CD, which are both able to form inclusion complexes with cytotoxic drug molecules such as doxorubicin and paclitaxel, nanocarriers with multimodal therapeutic

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• compounds for their anticancer activity [18]. The anticancer activity of compounds 3a–e was tested against five cell lines along with doxorubicin as positive control and all of them showed moderate to good anticancer effects. The results are collected in Table 3. The compounds whose IC50 values are observed

• ]. However, all prepared derivatives were observed to exhibit lower anticancer activity when compared to the reference drug doxorubicin which showed IC50 values in the range of 0.7 to 0.8 µM against the tested cell lines. Conclusion In conclusion, the synthesis of five novel methyl 10-undecenoate-based

• in triplicates and incubated for 24 h. The cells were then incubated with MTT (0.5 mg/mL) for 3 h and, to dissolve the insoluble formazan crystals, 100 µL DMSO was added to each well. Finally the absorbance of the plates was measured using a Synergy H1 multi-mode plate reader (USA). Doxorubicin was

Synthesis of a deuterated probe for the confocal Raman microscopy imaging of squalenoyl nanomedicines

• Eric Buchy,
• Branko Vukosavljevic,
• Maike Windbergs,
• Dunja Sobot,
• Camille Dejean,
• Simona Mura,
• Patrick Couvreur and
• Didier Desmaële

Beilstein J. Org. Chem. 2016, 12, 1127–1135, doi:10.3762/bjoc.12.109

• inhibitors [19] or doxorubicin [20]. For the elucidation of the mechanisms involved in the efficacy of these promising nanomedicines, the precise knowledge regarding the cellular uptake, the intracellular localization and the determination of the subcellular interactions and trafficking is crucial. To

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

• cell line but it was 2.3 fold less active than doxorubicin in vitro. Therefore, this article describes the synthesis of analogues of VI with different lipid, glycon and chalcone [25][26] tags to assay and evaluate their in vitro antimicrobial and cytotoxic activities against the above mentioned

• group of target cholesterols were screened in vitro as cytotoxic agents against the human prostate cancer cell line PC3 using the sulforhodamine B colorimetric (SRB) assay and doxorubicin as positive control (IC50 = 8.8 μM) (Figure 3) [48]. As shown in Figure 3, cholesterol–lactoside conjugate 27

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• weight (12–18000 Dalton) were obtained (Figure 6). Nano particles of the polymer were used for a controlled slow release of the drug doxorubicin (29) trapped in this material. Bhatia et al. used Novozyme 435 to make polymers from functionalized pentofuranose derivatives (i.e, 30) and PEG-600 dicarboxylic

• CAL-B catalysis. Bolaamphiphilic molecules containing (L)- and/or (D)-isoascorbic acid moieties. Doxorubicin (29) trapped in a polyester made of glycolate, sebacate and 1,4-butandiol units. Polyesters containing functionalized pentofuranose derivatives. Polyesters containing disulfide moieties

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers

• Milo Malanga,
• Mihály Bálint,
• István Puskás,
• Kata Tuza,
• Tamás Sohajda,
• László Jicsinszky,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3007–3018, doi:10.3762/bjoc.10.319

• used for layer-by-layer film formation [12]. The synthesis and characterization of a nanosized quaternary ammonium β-CD polymer with high load capacity of the anticancer drug doxorubicin has been described as well as its application as drug delivery carriers across the blood–brain barrier [13]. The

Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

• Kayoko Hayashida,
• Taishi Higashi,
• Daichi Kono,
• Keiichi Motoyama,
• Koki Wada and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2014, 10, 2756–2764, doi:10.3762/bjoc.10.292

• liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of

• the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome

• products. Keywords: cyclodextrins; doxorubicin; PEGylated liposome; polypseudorotaxane; sustained release; Introduction Cyclodextrins (CDs) are cyclic oligosaccharides comprising six (α-CD), seven (β-CD), and eight (γ-CD) glucopyranose units. They are characterized by a hydrophobic central cavity and a

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• such as vehicles (ethanol, propylene glycol), buffers (phosphate and citrate) and tonicity modifiers (NaCl, MgCl2) [118]. RF is also known to form complexes with dendrimers [103][119], certain drugs including antibiotics like cloxacillin sodium [102] and doxorubicin [120], dopamine [121], agents like N

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• . synthesized maleimide derivatives of doxorubicin and camptothecin. After intravenous administration these designed anticancer drugs bind rapidly to circulating albumin [17][18][19]. Endogenous albumin could be seen as a drug carrier, as it accumulates in solid tumors according to the pathophysiology of tumor

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• transduction in reporter cell lines containing either low or overexpressed NOD2 proteins. Probes 13 and 17 were also selective over the non-NOD-stimulated NF-κB pathways (TNF-α, doxorubicin and PMA/ionomycin) in these reporter assays. Both of the probes, and their close analogues as discovered through SAR

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• interactions between molecules with different lipophilicities and structures. The ability of cyclodextrin nanosponges to encapsulate drugs has been studied in depth for both hydrophilic and lipophilic molecules, including dexamethasone, flurbiprofen, doxorubicin, itraconazole, resveratrol, paclitaxel, 5

• nanosponges [37], reaching a percentage of less than 10% after 130 minutes. A similar result was obtained with the incorporation of doxorubicin in nanosponges. In in vitro tests, doxorubicin was released very slowly at pH 1.2 (about 1% after 120 minutes) and the percentage increased with pH values

• . Doxorubicin release of about 29% was obtained at pH 7.4. This behaviour could suggest that the nanosponge formulation is able to protect the drug from the gastric environment, allowing delivery in the intestinal tract. Vavia prepared nelfinavir mesylate loaded nanosponges to enhance the solubility of the drug

Syntheses and applications of furanyl-functionalised 2,2’:6’,2’’-terpyridines

• Jérôme Husson and
• Michael Knorr

Beilstein J. Org. Chem. 2012, 8, 379–389, doi:10.3762/bjoc.8.41

• -substituted terpyridines in biomedical sciences Furanyl-terpyridines were probed in biomedical sciences as cytotoxic molecules. Compounds 12 and 13 were tested as anticancer agents against seven different cell lines [4]. Their activities were compared to that of doxorubicin, which is a currently used

• anticancer agent. Additionally, their cytotoxicity against normal cells was evaluated (Table 3). As can be seen from Table 3, these furanyl-functionalised terpyridines display, in many cases, better cytotoxicity than doxorubicin. Unfortunately, they are also more toxic toward normal cells (RPTEC). Note that

• -functionalised tpys as potential biomolecule-labelling agents. Synthetic sequence envisioned for biomolecules labelling by click-chemistry. Influence of solvent on U/S ratio. Complexes obtained by direct oxidation of furanyl-functionalised tpys. GI50 (μg/ml) for terpyridines 12 and 13 compared to doxorubicin