α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• three steps. Biological studies Although approved for the treatment of CTCL, SAHA has been shown to display anticancer activity over a large range of other hematological and solid malignancies such as leukemia [24], lung cancer [25], cervical cancer (HeLa), breast cancer (MCF-7) [26], mesothelioma [27

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• envision a minimal model based on the previously reported accessible mRNA region of the class I histone deacetylase HDAC-1: 5’-GUGAGCCAAGAAACACUGCCU-3’ to investigate our photoswitchable PNAs [38]. Importantly, HDAC-1 is frequently overexpressed in tumors and particularly, in prostate cancer [39]. Results

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• -small cell lung cancer with ED50 values of 6.5 and 16.7 µg mL−1, respectively [71]. To obtain this interesting compound isolated from Dictyota dichotoma, C14 has to be modified with a keto function and the double bond between C3 and C4 has to be converted into an epoxide. Additionally, 3,7,18

• release of TNF-α by BALB/3T3 cells [75]. This cancer prevention activity can be initiated at an IC50 of only 2.5 µM. Other bioactive target molecules structurally accessible from compound 7 could be both epimers of (6R)-2,7,11-cembratriene-4,6-diol either 4S: α-CBT 16 or 4R: β-CBT 17 (Scheme 3). Both were

• isolated in 1985 from cigarette smoke condensate and identified as anticancer agents [76]. With quite similar potency (α-CBT: 25.2 µM and β-CBT: 21.9 µM [77]), they showed inhibition of the induction of Epstein–Barr virus early antigen by lymphoblastoid cancer cells. In the tobacco plant itself, both

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• Jessica Matthias Thines Kanagasundaram Klaus Kopka Carsten S. Kramer Max Planck Institute for Medical Research, Department of Optical Nanoscopy, Jahnstraße 29, 69120 Heidelberg, Germany Helmholtz International Graduate School, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 223, 69120

• Heidelberg, Germany Division of Radiopharmaceutical Chemistry, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 223, 69120 Heidelberg, Germany Institute of Inorganic Chemistry, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany German Cancer Consortium (DKTK), Heidelberg, Germany 10.3762/bjoc

• optical properties for medical and bioimaging. As a compound with intrinsic mitochondria targeting ability, the radiolabelled analogue can be applied in multimodal (PET/OI) imaging of mitochondria for diagnostic and therapeutic use in, e.g., cancer patients. Keywords: halogen-dance reaction

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• copper complexes have an interesting antiproliferative capacity towards a range of human cancer cell lines, inducing early apoptosis, followed by secondary necrosis [64]. The fluorescent analog having pyridine imine and PEG terminal functions shown in Scheme 7 has been synthesized with the aim of

• shown in Figure 11 was tested in vitro on human breast cancer cells MCF-7. One-photon absorption induced fluorescence demonstrated that this dendrimer is efficiently internalized after 3 h of incubation, more after 24 h, and was non-toxic at 50 μg mL−1 without irradiation. Two-photon irradiation was

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• following cell lines were used: mouse fibroblast cell line L929 (DSM ACC 2), human cervix carcinoma cell line KB-3-1 (DSM ACC 158), the human lung carcinoma cell line A549 (DSMZ ACC 107) and human breast cancer cell line MCF-7 (DSM ACC 115). The subconfluent cells were briefly washed with Earle’s Balanced

• ppm, J in Hz). For carbon numbering see Figure 1 and Figure 2. Antiproliferative activities in different cell lines. Data indicate EC50 values ± SD in µM. A549 = human lung carcinoma; L929 = mouse fibroblast; KB-3-1 = human cervix carcinoma; MCF-7 = human breast cancer cell line. Supporting

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• progressed into clinic for the treatment of pancreatic cancer and rheumatoid arthritis (RA) [61][62], respectively. In order to gain a comprehensive and deep understanding of the area and provide suggestions for triptolide’s future studies, the recent progress of the total syntheses was systematically

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• ] and was also found to be cytotoxic with localization to the endoplasmic reticulum [8]. The cytotoxicity of compound 2 prompted the preparation and evaluation of compound 2 conjugates with porphyrins [9] and steroids [10] for targeted uptake of compound 2 into cancer cells, and the conjugates showed

• described natural compound archangelolide (1) and its fluorescent dansyl conjugate 5 in primary, cancer and primary immune cells. First, we analyzed the rate of cell uptake of compound 5 and dansyl amide in U-2 OS (Figure 2 and Supporting Information File 1, Figure S18) and MRC-5 (Supporting Information

• In order to reveal whether compound 1 is as potent as thapsigargin or compound 2 in terms of inhibition of cancer cell proliferation, we evaluated its cytotoxicity in a number of cell lines originating from various tumors: prostate, osteosarcoma, breast, colon, pancreas and lung. Cells were treated

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

• 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

• -loaded FSSAs could be considered to deliver and release DOX in cancer cells. Conclusion In summary, an AB2-type host–guest-conjugated amphiphilic monomer, β-cyclodextrin-benzimidazole2 (β-CD-BM2), was successfully prepared to construct pH-responsive supramolecular self-assemblies. On the basis of the pH

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

• antigens and regulate the immune reaction by specific binding to CLRs. Therefore, compounds with expressed CRL agonist or antagonist properties could also be considered as potential agents for cancer immunotherapy [49][50]. Mannosylated liposomes with incorporated MDP have proved to be effective carriers

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• with a quinoline. Pyrroloquinolines have been found to show antibacterial and antifungal activity, to be ligands for the NK1 receptor, and to be effective against the Hif hypoxia pathway in cancer cell lines [36][37][38]. Almost all of the examples of dipolar cycloaddition reactions involving

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response

• Yu-Ying Wang,
• Yong Kong,
• Zhe Zheng,
• Wen-Chao Geng,
• Zi-Yi Zhao,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2019, 15, 1394–1406, doi:10.3762/bjoc.15.139

• time, directed by exploring biomedical applications of these compounds. Recently, we developed a series of guanidinium-modified calixarenes as novel artificial receptors [13][14]. We achieved ultrasensitive and specific fluorescence detection of lysophosphatidic acid (a cancer biomarker) by executing

• photoactivity of photosensitizers (PSs) were annihilated by the complexation of guanidinium-modified calix[5]arene pentadodecyl ether while reactivated by adenosine triphosphate (a cancer biomarker) displacement. This novel supramolecular phototheranostics strategy realized both tumor-selective imaging and

• ][27][58]. Nau and co-workers reported a SC4A–lucigenin IDA system to monitor the cell-uptake efficiencies of choline, acetylcholine and protamine [58]. Also, we reported a non-covalent fluorescence switch-on strategy for hypoxia imaging in cancer cells by utilizing the complex of a carboxyl-modified

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• shown nanomolar in vitro activities against chloroquine-sensitive and resistant strains of Plasmodium falciparum and can therefore be considered for the treatment of malaria [21]. Furthermore, similar derivatives have shown micromolar and submicromolar activity against 60 selected cancer cell lines

• , presumably by inhibition of microtubuli formation in cancer cells [22]. More specifically, a series of 60 1,3-diaryl-1-acylpyrazolines was tested as xanthine oxygenase inhibitors that can be efficacious against articular gout, cancer, and inflammation, with IC50 values of four derivatives in the range of 5.3

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

• ; Introduction Boron neutron capture therapy (BNCT) belongs to the so-called binary therapies for cancer treatment. It is based on the fission reaction after a low-energy neutron capture by a 10B atom. The neutron capture reaction gives rise to two high linear energy transfer (LET) particles (an α-particle and a

• not fully satisfactory owing to their rapid clearance from blood [2], their only moderate selectivity for cancer cells and short retention times in tumors. Therefore, research efforts are ongoing to synthesize new BNCT candidates with improved tumor selectivity and cell retention. The development of

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• sulfonyl fluorides in biological applications has been on the increase as evidenced by the number of recent publications [1][2][3]. One potential application of sulfonyl fluorides is as an 18F-radiolabelled synthon that can be conjugated to macromolecules and used to image cancer and other diseases in the

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

• , biopharmaceutical, biological, biomimetic (enzyme mimics, transport across membranes, ion channels, etc.) and biomedical (in cancer chemotherapy) applications, reviewed by Atwood et al. [15], Perret et al. [16], Da Silva et al. [17], Nimse et al. [18], Guo et al. [19], Agrawal et al. [20], Yousaf et al. [21]. The

Doebner-type pyrazolopyridine carboxylic acids in an Ugi four-component reaction

• Maryna V. Murlykina,
• Oleksandr V. Kolomiets,
• Maryna M. Kornet,
• Yana I. Sakhno,
• Sergey M. Desenko,
• Victoriya V. Dyakonenko,
• Svetlana V. Shishkina,
• Oleksandr A. Brazhko,
• Vladimir I. Musatov,
• Alexander V. Tsygankov,
• Erik V. Van der Eycken and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2019, 15, 1281–1288, doi:10.3762/bjoc.15.126

• discovery. The target products containing a heterocyclic core bound to a peptide-like chain also showed a broad spectrum of biological activity: β-secretase (BACE1) inhibitory activity [15]; inducing apoptosis in colorectal cancer cells [16]; antimalarial activity against a chloroquine (CQ) non-resistant

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• ]. Roniciclib, also named BAY 1000394, is a pan-cyclin-dependant kinase (CDK) inhibitor that contains an aryl cyclopropyl sulfoximine and that was developed to treat patients with untreated small cell lung cancer [6][9]. Aryl cyclopropyl sulfides 1 are also remarkable synthons in organic synthesis (Scheme 1

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• ]. Besides, several hybrid molecules containing, inter alia the oxindole moiety, have been discovered and they demonstrated diverse therapeutic activities, for example, against breast [46] and colon cancer cells [47] and drug-resistant bacteria [48]. Among the many excellent recent reviews on the preparation

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• uptake and breakdown, respectively. The association of galectins to cell signaling and adhesion gives them roles in several different pathological processes, such as pulmonary fibrosis [6][10], pathological lymphangiogenesis [11], inflammation [12] and cancer [13], with galectin inhibitors demonstrated

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• the disruptors of microtubule dynamics, therefore are of great interest in cancer drug discovery [6]. Thereby, the stereocontrolled total synthesis of marine alkaloids such as axinellamines [16] and the search of new 2-aminoimidazole and pyrrole containing compounds with a core structure that mimics

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• fentanyl, a powerful synthetic opioid commonly used for treatment of pain in cancer and postoperative patients (CDC). The recent emergence of fentanyl resulted in a 264% increase in synthetic opioid deaths within the U.S. from 2012 to 2015, due to the fact that users are often unaware of the presence of

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• convey specificity for prostate cancer cells. Keywords: calcium ATPase inhibitors; Heck- and Suzuki-coupling reactions; hydroquinones; prostate cancer; tethered amino acid; Introduction Sarco/endoplasmic reticulum calcium ATPase (SERCA) is an integral protein that resides in the membrane of the

• cytotoxic agent. The problem of concomitant toxicity to healthy cells has been circumvented by attaching a short peptide (His-Ser-Ser-Lys-Leu-Gln-Leu) to a tether at TG’s C-8 position (1b). This modification renders the inhibitor inactive [3]. Prostate cancer cells produce on their surface the serine

• protease PSA (prostate-specific antigen) that is capable of cleaving the peptide bond between Gln and Leu, thereby producing an active TG analogue that can enter the cancer cell and kill it by triggering apoptosis. Apoptosis occurs as the result of elevated cytosolic calcium levels, which are caused by

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

• -negative bacteria prevent the medical use of OMV from natural sources [4]. Licensed vaccines based on crude OMV are currently available to contribute to the prevention and to control at least twenty-five infections including pulmonary ones [5]. Developing synthetic vaccines against cancer [6][7] or Gram

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

• for 2b in benzene. The cytocidal effect of compound 2a on lung cancer cells under photolysis conditions was also assessed to test the efficacy as anticancer agents. In a medium containing 100 μg mL−1 of 2a exposed to light, the number of living cells decreased significantly compared to the unexposed

• described above, nitroxides are not toxic to normal host cells and exhibit toxicity only to tumor cells. Thus, nitroxides are ideal candidates as anticancer therapeutic agents. Based on this knowledge, the cytocidal effect of the radical released from compound 2a on lung cancer cells was tested in vitro, in

• vitro using lung cancer cells. One hundred thousand Lewis lung carcinoma (LLC) cells were seeded into 24-well plates (medium: DMEM) and incubated overnight at 37 °C under an atmosphere of 95% air and 5% CO2. The medium was replaced with fresh phenol-red free DMEM containing various concentrations of 2a