Microwave-assisted efficient one-pot synthesis of N²-(tetrazol-5-yl)-6-aryl/heteroaryl-5,6-dihydro-1,3,5-triazine-2,4-diamines

• Moustafa Sherief Moustafa,
• Ramadan Ahmed Mekheimer,
• Saleh Mohammed Al-Mousawi,
• Mohamed Abd-Elmonem,
• Hesham El-Zorba,
• Afaf Mohamed Abdel Hameed,
• Tahany Mahmoud Mohamed and
• Kamal Usef Sadek

Beilstein J. Org. Chem. 2020, 16, 1706–1712, doi:10.3762/bjoc.16.142

• [2], antitumor [3], anti-HIV [4], inhibitor of Trypanosoma brucei [5], angiogenesis inhibitor [6], antiplasmodial antifolates [7], and antimicrobial [8]. Moreover, and in particular N2,6-disubstituted-1,3,5-triazine-2,4-diamines possess a wide range of chemotherapeutic activities [8][9][10][11

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 and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• involved in the angiogenesis process [60]. Furthermore, the use of calixarenes for biological applications is the subject of intensive researches. They are indeed exploited in various areas such as surface recognition, structural mimes or membrane receptor inhibition [61][62][63], and it was also shown

• that calixarenes themselves display antibacterial, antiviral, and anticancer properties [64]. Herein, we describe the synthesis of a multivalent phototherapeutic agent designed in order to specifically target membrane receptors involved in the angiogenesis process. The multivalent system is composed of

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

• carcinogenesis is highly dependent on migration, invasion and angiogenesis renders integrins important anticancer targets. Integrin αvβ3 is an important factor in tumor angiogenesis and metastasis [45], two common characteristics of cancer that discriminates it from other diseases. Notably, integrin αvβ3 (also

• known as the vitronectin receptor) appears to be the most important among all integrins regarding cell proliferation, invasion and angiogenesis [47]. This integrin is overexpressed on activated endothelial cells, new-born vessels and other tumor cells [48][49], but it is found to be expressed at

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

• zinc-dependent metalloprotease that functions in cell proliferation, cell migration and angiogenesis [1][3][4]. However, it is known that the Asn-Gly moiety is subject to Asn deamidation through succinimide formation leading to isoaspartic acid (isoAsp, isoD) and aspartic acid derivatives usually in a

• ratio of 3:1 after hydrolysis [5][6][7][8][9][10][11]. IsoDGR peptides are bound to RGD-integrin receptors with high affinity [12][13][14]. Due to their function in tumor proliferation, metastasis and angiogenesis, integrin receptors are also promising targets for cancer therapy. Thus, NGR-peptide

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• significant anti-angiogenesis activity [31]. It is worth mentioning that this product has three consecutive stereocenters and different sites of variation from the original natural product. The hydride comes from the less hindered side of the ketone moiety, leading to the formation of a hydroxy group in cis

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• constituent of compounds with diverse applications, some of which display potent cytostatic activity through different mechanisms of action such as DNA intercalation, apoptosis, abrogation of cell migration, inhibition of angiogenesis and disregulation of nuclear receptor signaling [34][35]. Moreover, it was

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• suitable plastic dishes (ibiTreat µ-Slides Angiogenesis, ibidi, Martinsried, Germany). Vesicles were allowed to settle down some minutes before acquisition of z-stacks with 1 µm step size. Top: Chemical structures of cholesterol and hydroxycholesterols with selected numbering for the carbon atoms. The

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• that plays a key role in the regulation of several cellular processes, including apoptosis, DNA repair, and angiogenesis [1][2][3][4]. The murine double minute 2 (MDM2) protein is the primary cellular inhibitor of p53, functioning through direct interaction with p53 [5]: tumoral cells show an

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

• ]. The resulting disruption of protein–(glycosamino)glycan interactions had important biomedical consequences such as reduced selectin-mediated tumor cell adhesion [12][13], suppressed selectin-mediated leukocyte migration [11][14][15], reduced angiogenesis [3], or inhibition of tumor growth by decreased

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• the coumarin derivatives umbelliferone (4, Figure 1), esculetin (5, Figure 1), and scopoletin (6, Figure 1) are subject of anticancer research [67]. Marmesin (62) was first isolated from the fruits of Ammi majus [67], and is currently under investigation as an agent for the treatment of angiogenesis

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• relative drug preparations [5]. Icariin, icariside I (2), and their aglycone, icaritin (3) (Figure 1), possess multiple biological activities, such as anti-oxidative [6], anti-inflammatory [7], anti-osteoporotic [8], anticancer [9], neuroprotective [10], angiogenesis stimulating [11], testosterone mimetic

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

• these parameters [76][79]. A delivery system should therefore ideally fulfill certain requirements. It should be biological and immunological inert; promote specific cell adhesion, proliferation, and angiogenesis; provide growth factors; be rigid to withstand deforming forces (depending on application

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

• described. Keywords: angiogenesis; natural phenolic compounds; structure–activity relationship; synthesis; Introduction The term angiogenesis is commonly used to describe the biological process of blood vessel growth. Nevertheless, it should be more precisely defined as the formation of new blood vessels

• from preexisting ones. Under physiological conditions, angiogenesis is vital for foetal development, tissue regeneration and wound healing. From a pathophysiologic perspective, massive vascular growth or abnormal shape formation promotes many ailments including cancer, inflammation, and eye illnesses

• metastases. Nevertheless, the morphology and pathophysiology of these blood vessels differs significantly from physiological ones as they are less effective and show a lower state of organization and control [3]. Since the discovery of the mechanism of angiogenesis and its crucial role in tumor development

2-(1-Hydroxypropyn-2-yl)-1-vinylpyrroles: the first successful Favorsky ethynylation of pyrrolecarbaldehydes

• A. V. Ivanov,
• V. S. Shcherbakova,
• I. A. Ushakov,
• L. N. Sobenina,
• O. V. Petrova,
• A. I. Mikhaleva and
• B. A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 228–232, doi:10.3762/bjoc.11.25

• ] and novel cyclin-dependent kinase inhibitors [2]. Such functionalized pyrroles are intermediates for endothelial differentiation gene (EDG-1) receptor antagonists. The latter are effective in preventing and/or treating inflammations, diseases associated with abnormal angiogenesis, cerebral vascular

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• with various physiological and pathological processes such as morphogenesis, angiogenesis, tissue repair, cirrhosis, arthritis, and metastasis, thus raising the possibility that inhibitors of these enzymes may possess therapeutic potential [112][113]. As part of studies on conformationally constrained

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• , apoptosis, angiogenesis, and B cell activation [8][9][10]. Galectin-3 has been reported to be involved in mechanisms that cluster cell surface glycoproteins [10][11], cross-link receptors [12], and form lattices and larger aggregates [13]. Structurally, galectin-3 is composed of one carbohydrate recognition

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• , anticancer and anti-angiogenesis activities, which are probably caused by the inhibition of threonyl-tRNA synthetase and apoptosis induction by caspase activation [1][2][3][4]. It bears several unusual structural elements like a cyclopentane ring and a carbonitrile (Figure 1a), which are built-up by

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

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

• glycogen synthase kinase 3 (GSK-3), a key regulator of both differentiation and cellular proliferation [9]. An alternative antitumor strategy involves the inhibition of processes involved in tumor growth, e.g., angiogenesis. Integrin αvβ3 is a receptor that has been found on the surface of many tumor cells

• and recognizes the arginine–glycine–aspartic acid (RGD) sequence. Antagonists of this receptor are able to inhibit angiogenesis. 1,2,4-Oxadiazolebutanoic acids such as C were tested as non-peptidic analogs of αvβ3 antagonists [10]. Furthermore, substituted 1,2,4-oxadiazoles have been described as

Synthesis of 5-(ethylsulfonyl)-2-methoxyaniline: An important pharmacological fragment of VEGFR2 and other inhibitors

• Miroslav Murár,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2013, 9, 173–179, doi:10.3762/bjoc.9.20

• -(ethylsulfonyl)-2-methoxy-1,3-dinitrobenzene (4a) have been precisely physicochemically characterised. Keywords: angiogenesis; pharmacophoric ligand; synthesis of 5-(ethylsulfonyl)-2-methoxyaniline; VEGFR2 tyrosine kinase inhibitors; Introduction 5-(Ethylsulfonyl)-2-methoxyaniline (5) is a starting material

• kinase 1, alpha and beta adrenoreceptors, glycogen phosphorylase, IMP dehydrogenase, MMPs 2, 3, 9 and 13, etc. [1]. Vascular endothelial growth factor (VEGF-A) is a homodimeric glycoprotein and thought to be the key signalling molecule of angiogenesis, i.e., the formation of new blood vessels from pre

• -existing ones. Angiogenesis is essential for cancers to develop from a small size. VEGF-A binds to two VEGF receptors that are expressed on the surface of vascular endothelial cells (VEGF receptor-1 and VEGF receptor-2). New vasculature is formed in and around the tumour, allowing it to grow exponentially

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis. The most active compound, (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF

• . In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis

• (hydroxymethyl)furan and benzoylated galactose imidate, is nontoxic and antagonizes cell physiological processes in vitro that are important for the dissemination and growth of tumor cells in vivo. Keywords: angiogenesis; biomimetic synthesis; carbohydrates; in silico blind docking; melanoma cells

Stereoselective synthesis of four possible isomers of streptopyrrolidine

• Debendra K. Mohapatra,
• Barla Thirupathi,
• Pragna P. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2011, 7, 34–39, doi:10.3762/bjoc.7.6

• % yield over six steps starting from D-phenylalanine and L-phenylalanine, respectively. The absolute configuration of the natural product was shown to be (4S,5S) by comparing its spectral and analytical data with the reported values. Keywords: aldol reaction; angiogenesis; cancer; Lewis acid mediated

• generally considerable associated toxicity, often with limited success. Therefore, more universal, more effective, and less toxic therapeutic agents are desirable. Recently, inhibition of angiogenesis has been considered as a desirable pathway for preventing tumor growth and metastasis, primarily because of

• the low potential for toxicity or resistance [2], as well as the potential for treating a broad spectrum of tumor types, arthritis, and psoriasis [3][4][5][6][7][8]. For this reason, angiogenesis inhibition has become an active area of pharmaceutical research, and over 40 such agents are currently