One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• IV inhibitor carmegliptin (2, DPP IV) with potential for the treatment of type-II diabetes [3][4]. A comparative study on novel classes of anticancer drugs identified benzo[a]quinolizines 3 and 4 (Figure 1) to be useful for a specific inhibition of heat shock response in cancer cells, which strongly

• enhances the treatment by sensitizing cancer cells to anticancer drugs [5]. The presence of such structural pattern has driven the development of various approaches for its obtaining – based either on isolation from naturally occurring sources or through multistep synthetic routes [6]. The pyrrolo[2,1-a

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• (Taxotere®) both are anticancer drugs of the taxoid series. They inhibit cell growth through the interaction with microtubules. In order to study the structure–activity relationships, the D-ring-modified deoxythiataxoid 154a was synthesized. For this, the iodomethyloxirane derivative 152 was first treated

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• are nowadays incorporated into drug scaffolds of compounds either licensed or currently being studied in clinical trials. Categories I–V of fluorinated phenylalanines. Structures of PET radiotracers of 18FPhe derivatives. Structures of melfufen (179) and melphalan (180) anticancer drugs. Structure of

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• structural changes of the nucleic acid. In turn, both of these processes interfere with biologically relevant recognition processes between DNA and enzymes, e.g., topoisomerase [10]. Therefore, many potential lead structures of chemotherapeutic anticancer drugs exhibit DNA-binding properties [1][2][3][4][5

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• differential for tumor cells. Members of one prominent novel class of targeted anticancer drugs that has been developed over the last years are antibody–drug conjugates (ADCs) [9][10][11]. Due to their high antibody-mediated target specificity, ADCs are designed for selective treatments of tumor cells with

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

• of sequences have been designed for addressing and delivering anticancer drugs to the nuclei and its subnuclear regions. Although several drugs might be delivered successfully inside a cell, they often fail since they are not able to reach their subcellular target. In order to circumvent adverse side

• described as beneficial tools in the creation of anticancer drugs [21]. Within this study, we aimed to design novel efficient cell-penetrating peptides that preferentially locate within cell nuclei and subnuclear regions. For this, we generated peptide chimera consisting of a shortened version of the

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

• -rich sequences [41][42]. However, clinical development of TAM was discontinued due to severe myelotoxicity. With distamycin, netropsin and TAM as the lead compounds for novel anticancer drugs, a plethora of oligopyrrole derivatives were reported with the aim of increasing stability, greater DNA binding

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

• intervention, radiation and chemotherapy. Drugs used for this purpose are inevitably cytotoxic in order to eliminate cancer cells, but they lack selectivity that could be developed through targeting malignant cells (Figure 1). Due to the uncontrolled peripheral toxicity, anticancer drugs usually kill healthy

• 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

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

• homing devices may provide dual targeted delivery of anticancer drugs. According to literature data, one of the most stable and tumor-selective cyclic NGR-peptides is c[KNGRE]-NH2, in which the α-amino group of the N-terminal Lys is coupled to the γ-carboxyl group of the glutamic acid residue (head-to

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

• Debrecen, 4032 Debrecen, Hungary 10.3762/bjoc.14.64 Abstract Gonadotropin releasing hormone-III (GnRH-III), a native isoform of the human GnRH isolated from sea lamprey, specifically binds to GnRH receptors on cancer cells enabling its application as targeting moieties for anticancer drugs. Recently, we

• (Dox), daunorubicin (Dau) or epirubicin are frequently used anticancer drugs. Their mode of action is based on a planar ring system which is important for intercalation into DNA [10]. In this way, anthracyclines can affect a broad range of DNA processes leading to an inhibited synthesis of

Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis

• Anna Kuźnik,
• Roman Mazurkiewicz and
• Beata Fryczkowska

Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269

• anticancer drugs, antioxidants, or functional probes into the mitochondria [5][6][7][8]. Review 1. Synthesis of vinylphosphonium salts 1.1. Alkylation of phosphines with alkyl halides One of the most common methods for the preparation of vinylphosphonium salts 1 is the quaternization of vinylphosphines with

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

• enhancement of MOF structural and stability properties [90][91]. Bioactive molecules like caffeine [92][93] and anticancer drugs [94][95][96][97][98] were incorporated in ZIF-8 and tests proved that these systems allowed for a controlled drug release. Further studies involving ZIF-8 with encapsulated

• anticancer drugs have also shown that these have potential to be used in fluorescence imaging. The number of reports on MOFs synthesized by mechanochemistry [8][28][50][99][100][101] has been increasing and some in situ studies on the mechanosynthesis of MOFs and coordination polymers are already being

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

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

• metal-based anticancer drugs need to be developed. Recently, it has been reported the interesting synthesis of AuNPs coated with glyco-polymers and functionalized with gold(I) triphenylphosphine (Figure 7) [88]. This work showed the potentiality of these structures as novel cancer therapeutic drugs. The

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• as antiviral and antibacterial agents [5] (I and II), anticancer drugs [6] (VI), pharmaceuticals used in the Alzheimer’s disease treatment [7] (III), cardiovascular drugs [7] (IV), insecticides, fungicides, herbicides [8] (V) and non-nucleoside, low molecular drugs for the hepatitis C treatment

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• agents and initiators for free-radical reactions both in industry and in laboratory. These compounds are produced and involved in various natural and biological processes and were explored extensively as antimalarial agents, anthelmintics, and anticancer drugs. Organic peroxides, such as alkyl

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• cell growth creates an avenue for their use in the development of anticancer drugs, it also limits their utility as agents to modify the cellular glycome [62]. The cytotoxic activity of peracetylated monofluoro analogs 1, and 4–6, their 1-O-deacetylated derivatives 2, and 49–51, difluoro analogs 7 and

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• treatment. Plants also have an important role as a source of antitumoral agents, and several anticancer drugs currently in use are derived from natural sources. Natural products often have selective biological actions due to binding affinities for specific proteins, and have superior chemical diversity and

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

• reactions on the 6-chloropurine nucleosides. Intermediate compounds 31–40 were deprotected with a saturated solution of ammonia in methanol to furnish the desired products 6–15 in 70–92% yields (Table 1). 3’-Fluoro-2-chloropurine nucleosides – cladribine and clofarabine mimics Anticancer drugs cladribine

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

• and death. This explains why it is down-regulated during carcinogenesis and opens the door for nucleophilic addition of amines to 5,6α-EC as a new lead for developing potential anticancer drugs [15]. Apart from antimicrobial and antiproliferative activities of cholesterol derivatives, other

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• selectivity according to the reported IC50 data. A linear or angular arrangement, as found in ascididemin and neoamphimedine structures, respectively, are two interesting backbones that could be used as starting points in the search for new anticancer drugs. Pyridoacridones containing fused rings with 1,4

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• previously [60]. A2058 cells are highly invasive human epithelial adherent melanoma cells, derived from lymph nodes metastatic cells obtained from a 43 year old male patient. They are tumorigenic at 100% frequency in nude mice, and considered as very resistant to anticancer drugs. All cell culture

Gold-catalyzed formation of pyrrolo- and indolo-oxazin-1-one derivatives: The key structure of some marine natural products

• Sultan Taskaya,
• Nurettin Menges and
• Metin Balci

Beilstein J. Org. Chem. 2015, 11, 897–905, doi:10.3762/bjoc.11.101

• and multidrug resistance reversal activity [12][13][14]. Lamellarins 4 with a pyrrolo-oxazinone substructure are also marine natural products and they inhibit the proliferation of cancer cells and therefore are promising candidates for anticancer drugs [15][16][17][18][19][20]. The design and

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

• 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

• is the poor aqueous solubility due to the hydrophobicity of most anticancer drugs [3]. Most of the anticancer drugs are formulated with co-solubilizers via intravenous administration; however these co-solubilizers lead to severe side effects restricting both the patient’s quality of life and efficacy

• of the therapy. Another major factor is that anticancer drugs have a wide distribution capacity in the body and owing to non-selective cytotoxicity of these drugs not only the cancer cells but also healthy cells are killed. Due to low therapeutic indices of anticancer drugs, a rapid increase and

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

• delivery of anticancer drugs [28]. PEG-LP encapsulating DOX is commercially available as DOXIL/CAELYX® [28]. In addition, PEG-LPs are also utilized as long-circulating drug carriers for protein drugs and nucleic acids [37][38]. Thus, PEG-LPs are representative drug carriers and CD PPRXs of PEG-LPs could be