Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• , angiogenesis, and metastasis in cancer [12][13][14][15], pointing at bisphosphonates as potential treatments for cancer and other inflammation-related diseases. In this respect, MMP inhibition by phosphonates or bisphosphonates has been previously studied through computational or X-ray diffraction analyses to

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• , Boston, MA 02125, USA Department of Cancer Biology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA School of Chemistry, Biology and Materials Engineering, Suzhou University of Science and Technology, Suzhou 215009, China 10.3762/bjoc.16.106 Abstract

Synthesis and anticancer activity of bis(2-arylimidazo[1,2-a]pyridin-3-yl) selenides and diselenides: the copper-catalyzed tandem C–H selenation of 2-arylimidazo[1,2-a]pyridine with selenium

• Mio Matsumura,
• Tsutomu Takahashi,
• Hikari Yamauchi,
• Shunsuke Sakuma,
• Yukako Hayashi,
• Tadashi Hyodo,
• Tohru Obata,
• Kentaro Yamaguchi,
• Yasuyuki Fujiwara and
• Shuji Yasuike

Beilstein J. Org. Chem. 2020, 16, 1075–1083, doi:10.3762/bjoc.16.94

• appropriate quantity under otherwise identical reaction conditions. The prepared selenides and diselenides bearing two imidazo[1,2-a]pyridine rings were all novel compounds. Among the prepared diselenides and selenides that exhibited cytotoxicity against cancer cells, bis[2-(4-methoxyphenyl)imidazo[1,2-a

• reductive elimination to afford the diselenide 2. The anticancer activity of the novel synthesized bis(2-arylimidazo[1,2-a]pyridin-3-yl) diselenides 2 and selenides 3 was evaluated in human cervical cancer HeLa cells (Figure 5). At 25 µM, each compound significantly decreased the cell viability compared to

• Figure 6, 2f also exhibited cytotoxicity against U251 human glioblastoma cells and HKBMM human malignant meningioma cells. Importantly, the diselenide 2f was more cytotoxic toward HeLa cancer cells than to human brain microvascular endothelial (HBME) cells, which are noncancerous (Figure 7). Hence, the

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

• yields of 25–35% and with a radiochemical purity of more than 99%. The 18F-labeling of 4-borono-ᴅ,ʟ-phenylalanine (BPA) provided a potential tool for cancer treatment by boron neutron capture therapy [53] (Scheme 16). The syntheses of a variety of clinically relevant radiotracers including protected 4

• . demonstrated its inhibitory activity of gastrin-stimulated growth of pancreatic cancer both in vitro and in vivo studies [110] (Figure 4). 5.2.3. Dual CCK1/CCK2 receptor antagonists: Johnson & Johnson identified compound 182 as a dual CCK1/CCK2 receptor antagonist with desirable pharmacologic properties [51

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• example, in anti-HIV therapy, MUC1-based antitumor vaccines, or as antibiotics [12][13][14]. Especially glycans bearing noncanonical amino acids, which can only be introduced into a peptide by organic synthesis, are suitable for cancer therapy since they show better resistance to enzymatic degradation in

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• constitute a broad family of natural macrolides that act as powerful cytotoxic agents against various cancer cell lines. Due to the stereochemical intricacy and high cytotoxicity, these compounds have attracted a great deal of attention from synthetic chemists. The application of an intermolecular enyne

• , thereby affording the triene intermediate in a substantial yield. Additional transformations using conventional methods efficiently provided (−)-amphidinolide E (3). Amphidinolide K, another important bioactive macrolide endowed with specific cytotoxic activity against L1210 and KB cancer cells, was also

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• differentiation, cell cycle progression and apoptosis by targeting both histone and non-histone proteins. The balance between acetylation and deacetylation is pivotal for typical cell function. Abnormal or increased HDAC expression has been reported in several human tumors and cancer cell lines [2]. As such, the

• interests are Class I HDAC isozymes, HDAC2 and HDAC8, which are important targets in cancer models as both are associated with high risk diseases such as prostate cancer and neuroblastoma [6][7][8]. Compounds such as vorinostat, givinostat and panobinostat have been successfully applied as HDAC inhibitors

• in anticancer efforts. Although panobinostat offers a versatile approach for the inhibition of cancer cell growth and survival, a lack of selectivity and bioavailability can cause negative molecular and clinical effects, specifically in combination therapies. Despite advances in Class I HDAC

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• delivery [93], and cancer detection [94]. In this regard, various functionalized MNPs were employed in diverse organic reactions, including Suzuki–Miyaura reactions, Sonogashira reactions, Ullmann coupling, hydrogenation reactions, oxidation reactions, hydroformylation reactions, and “click” reactions [89

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• nm occurs almost quantitatively. This can be seen as one big feature of NIR absorbers; that is the function of a “molecular oven/furnace” whose operation bases on a photonic process, which can be easily turned ON or OFF by operation of the light source. Medical applications with focus on cancer

Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus

• Amit Raj Sharma,
• Enjuro Harunari,
• Naoya Oku,
• Nobuyasu Matsuura,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 297–304, doi:10.3762/bjoc.16.29

• eggplant calyx induces apoptosis in human ovarian cancer cells, leading to cell death [33]. One example of a keto fatty acid from the animal kingdom is (E)-9-oxo-2-decenoic acid, a sex pheromone found in royal jelly. Queen honey bees use this fatty acid to control the activity of worker bees [34]. (E)-7

Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin

• Thomas J. Cogswell,
• Craig S. Donald and
• Rodolfo Marquez

Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15

• be cytotoxic against human leukaemia, kidney, ovarian and prostate cancer cell lines (IC50 = 25 µM, U251 cell line) [14][15][16]. In an attempt to increase the bioavailability of (R)-(+)-goniothalamin 2, aza-goniothalamin 1 was designed and synthesised; however, aza-goniothalamin 1 was found to have

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• for antimitotic potency in cellulo, since the degree of resazurin turnover scales to the number of cells still viable after compound treatment, although the mechanism behind antiproliferative activity must later be determined using more specific assays. We used the HeLa human cervical cancer cell line

The interaction between cucurbit[8]uril and baicalein and the effect on baicalein properties

• Xiaodong Zhang,
• Jun Xie,
• Zhiling Xu,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 71–77, doi:10.3762/bjoc.16.9

• , anti-allergic, antispasmodic, diuretic and anticancer [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]. For example, baicalein can play an antitumor effect on lung cancer by inducing cell apoptosis, blocking cell cycle and inhibiting metastasis of lung cancer, but it

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• compounds against cancer cells, the modifications implemented in series i, ii and iii are the most effective strategies so far to enhance the phototherapeutic indices. The present evaluation identifies peptides 2, 4, 7, 8, and 13 as the best candidates in terms of the phototherapeutic index. Conclusion In

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• hexacarbonyl complexes; Nicholas reaction; nucleosides; propargyl cation; Introduction Nucleoside analogs are molecules of high pharmacological interest for the treatment of various conditions, especially cancer and viral diseases [1][2][3][4][5]. The substitution at C-5 of the uracil nucleobase provides a

• hexacarbonyls with 2'-deoxyuridines revealed pronounced in vitro activity against MCF-7 and MDA-MB-231 human breast cancer cells [32][33]. A recent investigation of hexacarbonyl dicobalt adducts of nucleosides containing derivatives of propargyl alcohol demonstrated their antiproliferative activities for the

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• anticholinergic agent for its antimuscarinic effects [3][17]; apigenin can function as an antiviral drug for the treatment of HIV [18][19], cancer [20][21][22], and other viral infections [23]; pranlukast [24] can be used in the treatment of allergic rhinitis [25] and asthma [26]; and khellin [27] has been proved

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• Abstract Terpenoids are the largest and structurally most diverse class of natural products. They possess potent and specific biological activity in multiple assays and against diseases, including cancer and malaria as notable examples. Although the number of characterized terpenoid molecules is huge, our

• . Taxol (1), a plant-derived terpenoid, provides an illustrative example. Taxol was structurally characterized in 1971 [4] and approved by the FDA as an anticancer agent in 1992 [13]. Today, almost 50 years after its initial report, despite its blockbuster status in cancer therapy [14] and multiple

Preparation of anthracene-based tetraperimidine hexafluorophosphate and selective recognition of chromium(III) ions

• Qing-Xiang Liu,
• Feng Yang,
• Zhi-Xiang Zhao,
• Shao-Cong Yu and
• Yue Ding

Beilstein J. Org. Chem. 2019, 15, 2847–2855, doi:10.3762/bjoc.15.278

• autoimmune and cardiovascular diseases [11]. On the other hand, the excessive incorporation of chromium(III) is toxic to humans, and can cause cancer through the oxidation of DNA and some proteins [12][13][14]. Therefore, the detection of chromium(III) has a vital practical significance for human health

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• ]. The isozymes of NPPs are involved in the pathophysiology of different diseases, such as calcification, cancer, and insulin resistance [34][35]. All derivatives of compounds 5 were tested for human recombinant NPPs, i.e., NPP1–3. In addition, we compared the obtained results with those of recently

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• Institute is core funded by Alzheimer’s Research UK (520909). The Francis Crick Institute receives its core funding from Cancer Research UK (FC001002), the UK Medical Research Council (FC001002), and the Wellcome Trust (FC001002). We thank our colleagues Sarah Frew, Amy Monaghan, Fiona Jeganathan and Magda

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• Sciences) and cultured according to standard mammalian tissue culture protocols and sterile technique. Human cancer cell lines HEK293 and HeLa were obtained from the HPA Culture Collections (UK). All cell lines used in the study were tested and shown to be free of mycoplasma and viral contamination. Cell

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• conversions [7]. Porphyrins have been extensively studied as potential photosensitizers in a photodynamic therapy (PDT) [8][9], a promising treatment modality for several cancer and infectious diseases. In PDT, light, O2, and a photosensitizing drug are combined to produce a selective therapeutic effect via

• spectroscopy and mass spectrometry. These novel porphyrins and chlorins are expected to be efficient photosensitizers for cancer treatment. The presence of four maleimide groups in these compounds may provide improved binding with proteins in living systems. Synthesis of fluorinated maleimide-substituted

Plasma membrane imaging with a fluorescent benzothiadiazole derivative

• Pedro H. P. R. Carvalho,
• Jose R. Correa,
• Karen L. R. Paiva,
• Daniel F. S. Machado,
• Jackson D. Scholten and
• Brenno A. D. Neto

Beilstein J. Org. Chem. 2019, 15, 2644–2654, doi:10.3762/bjoc.15.257

• previously stained with the fluorescent compound. There is no way to eliminate this fluorescent signal because of the constitutive presence of endosomes in mammalian cells. Cancer cells have, in addition, an accelerated metabolism and high endocytosis index [63]. Endocytosis is known to be the cellular event

• . Biological experiments. The new BTD derivative BTD-4APTEG was diluted in water in the cell medium supplemented with 10% of fetal calf serum. The following cell lines were used: human ovarian cancer cell line A2780, human breast adenocarcinoma cell line MCF-7, breast adenocarcinoma cell line T47D and human

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• potential cancer target. Further structure–activity relationship studies are required to fully characterise this potential anticancer pharmacophore. This study again demonstrates how taxonomy-guided exploration of fungi is a highly effective strategy for identifying novel bioactive metabolites. Experimental

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• clinical trials against colon cancer, gall bladder cancer and acute myelogenous leukemia in humans [40] and its 2-aza analogue 3 is also active against human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) [41]. To the best of our knowledge, this case of α-imino silver-carbene is not yet