18523-48-3Relevant articles and documents
Rhenium(I) polypyridine dibenzocyclooctyne complexes as phosphorescent bioorthogonal probes: Synthesis, characterization, emissive behavior, and biolabeling properties
Choi, Alex Wing-Tat,Liu, Hua-Wei,Lo, Kenneth Kam-Wing
, p. 2 - 10 (2015)
We report the development of rhenium(I) polypyridine complexes appended with a dibenzocyclooctyne (DIBO) moiety as bioorthogonal probes for azide-modified biomolecules. Three phosphorescent rhenium(I) polypyridine DIBO complexes [Re(N^N)(CO)3(py-C6-DIBO)][CF3SO3] (py-C6-DIBO = 3-(N-(6-(3,4:7,8-dibenzocyclooctyne-5-oxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N = 1,10-phenanthroline (phen) (1a), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4-phen) (2a), 4,7-diphenyl-1,10-phenanthroline (Ph2-phen) (3a)) and their DIBO-free counterparts [Re(N^N)(CO)3(py-C6-BOC)][CF3SO3] (py-C6-BOC = 3-(N-(6-(tert-butoxycarbonylamino)hexyl)aminocarbonyl)pyridine; N^N = phen (1b), Me4-phen (2b), Ph2-phen (3b)) were synthesized and characterized. Upon photoexcitation, all the complexes displayed intense and long-lived yellow triplet metal-to-ligand charge-transfer (3MLCT) (dπ(Re) → π?(N^N)) emission. The DIBO complexes underwent facile reactions with benzyl azide in methanol at 298 K with second-order rate constants (k2) in the range of 0.077 to 0.091 M- 1 s- 1. As revealed from SDS-PAGE analysis, the DIBO complexes can selectively label azide-modified proteins and the resulting bioconjugates displayed strong phosphorescence upon photoexcitation. Results of inductively coupled plasma mass spectrometry (ICP-MS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the DIBO complexes accumulated in Chinese Hamster Ovary (CHO) cells with considerable cytotoxic activity. Upon incubation of CHO cells with these complexes, relatively weak intracellular emission was observed. In contrast, upon pretreatment of the cells with 1,3,4,6-tetra-O-acetyl-N-azidoacetyl-d-mannosamine (Ac4ManNAz), intense emission was observed from the cell membrane and some internal compartments. The results suggest that the DIBO complexes are promising candidates for imaging azide-labeled biomolecules.
Moxifloxacin/Gatifloxacin-1,2,3-triazole-isatin Hybrids with Hydrogen-Bond Donor and Their In Vitro Anticancer Activity
Chen, Rongxing,Zhang, Hao,Ma, Tianwei,Xue, Huarui,Miao, Zhong,Chen, Liyan,Shi, Xiangkui
, p. 2691 - 2694 (2019)
A series of novel moxifloxacin/gatifloxacin-1,2,3-triazole-isatin hybrids (8a–i) were designed, synthesized, and screened for their in vitro anticancer activity in this paper. All of the synthesized hybrids were active against A549 and HepG2 cancer cell lines, whereas the parent drugs moxifloxacin and gatifloxacin were devoid of activity. Among them, hybrid 8i (IC50: 41.1–98.3 μM) showed considerable activity against A549, HepG2, and MCF-7 cancer cell lines, and it was no inferior to Vorinostat (IC50: 64.32 to >100 μM) against the three cancer cell lines. Thus, this kind of hybrids has potentiality for discovery of new anticancer candidates for clinical deployment in the control and eradication of cancers.
Novel N-acetyl-Glycol-split heparin biotin-conjugates endowed with anti-heparanase activity
Esposito, Emiliano,Vlodavsky, Israel,Barash, Uri,Roscilli, Giuseppe,Milazzo, Ferdinando M.,Giannini, Giuseppe,Naggi, Annamaria
, (2020)
Heparanase is regarded as a promising target for anticancer drugs and Ronepastat is one of the most promising heparanase inhibitors insert in clinical study for Multiple Myeloma Therapy. To improve its pharmacokinetic/pharmacodynamic profile, as well to have an antidote able to neutralize its activity in case of over dosages or intolerance, a new class of its derivatives was obtained inserting non-carbohydrate moieties of different length between the polysaccharide chain and biotin or its derivatives. In vitro these novel derivatives maintain the anti-heparanase activity without induced toxicity. The newly synthesized compounds retained the ability to attenuate the growth of CAG myeloma tumors in mice with potency similar, or in one case even higher than that of the reference compound Roneparstat as well as inhibited metastatic dissemination (lung colonization) of murine B16-F10 melanoma cells in vivo.
Supramolecular dendrimers: Convenient synthesis by programmed self-assembly and tunable thermoresponsivity
Ghosh, Partha S.,Hamilton, Andrew D.
, p. 2361 - 2365 (2012)
We report here the noncovalent synthesis of thermosensitive dendrimers. Short oligoguanosine strands were linked to the focal point of a dendron by using "click chemistry", and quadruplex formation was used to drive the self-assembly process in the presence of metal ions. The dynamic nature of these noncovalent assemblies can be exploited to create combinatorial libraries of dendrimers as demonstrated by the co-assembly of two components. These supramolecular dendrimers showed thermoresponsive behavior that can be tuned by varying the templating cations or the number of guanines in the oligonucleotide strand. Copyright
A Merged Aldol Condensation, Alkene Isomerization, Cycloaddition/Cycloreversion Sequence Employing Oxazinone Intermediates for the Synthesis of Substituted Pyridines
Williamson, Jill B.,Smith, Emily R.,Scheerer, Jonathan R.
, p. 1170 - 1172 (2017)
A domino reaction sequence has been evaluated that begins with union of novel dihydrooxazinone precursors with 2-alkynyl-substituted benzaldehyde components through aldol condensation. Ensuing operations, including alkene isomerization, Diels-Alder, and retrograde Diels-Alder with loss of CO 2 occurs in the same reaction vessel to provide polysubstituted tricyclic pyridine products.
Synthesis and biological evaluation of moxifloxacin-acetyl-1,2,3-1H-triazole-methylene-isatin hybrids as potential anti-tubercular agents against both drug-susceptible and drug-resistant Mycobacterium tuberculosis strains
Gao, Feng,Chen, Zijian,Ma, Long,Fan,Chen, Linjun,Lu, Guangming
, p. 648 - 655 (2019)
Herein, synthesis and biological evaluation of fourteen moxifloxacin-acetyl-1,2,3-1H-triazole-methylene-isatin hybrids as potential anti-tubercular agents against both drug-susceptible (MTB H37Rv), rifampicin-resistant and multidrug-resistant Mycobacterium tuberculosis strains were reported, and cytotoxicity towards VERO cells as well as inhibitory activity against MTB DNA gyrase were also discussed in this paper. The structure-activity relationship and structure-cytotoxicity relationship demonstrated that substituents on the C-3 and C-5/C-7 positions of isatin framework were closely related with the anti-mycobacterial activity and cytotoxicity. The most active hybrids 8h and 8l (MIC: 0.12–0.5 μg/mL) showed excellent activity which was no inferior to the parent moxifloxacin against the tested drug-susceptible, rifampicin-resistant and multidrug-resistant Mycobacterium tuberculosis strains, demonstrating their potential application as novel anti-tubercular candidates.
Design and synthesis of cyclo[-Arg-Gly-Asp-Ψ(triazole)-Gly-Xaa-] peptide analogues by click chemistry
Liu, Yaqin,Zhang, Lihui,Wan, Jieping,Li, Yesen,Xu, Yuhong,Pan, Yuanjiang
, p. 10728 - 10734 (2008)
A simple and mild synthesis of a new family of cyclopeptide analogues cyclo[-Arg-Gly-Asp-Ψ(triazole)-Gly-Xaa-] that is obtained by cyclization with click chemistry was investigated. In addition, the method was also successfully expanded to the synthesis of their analogues of different ring sizes. The result supports the potential utility of click chemistry in the preparation of novel integrin domain-binding antagonists and other cyclopeptide analogues.
Design of phosphonate analogs of short peptides by “click” chemistry
Artyushin,Sharova,Yarkevich,Genkina,Vinogradova,Brel
, p. 2172 - 2177 (2016)
Methods were developed for the first time for the modification of the natural neuropeptides Ile–Gly–Leu and Leu–Gly–Leu simultaneously with the phosphonate moiety and the triazole ring or solely with the triazole ring by means of click chemistry. All of the peptidomimetics synthesized were isolated as a mixture of diastereomers and were characterized by spectroscopic methods.
Spontaneous Single-Crystal-to-Single-Crystal Evolution of Two Cross-Laminated Polymers
Athiyarath, Vignesh,Sureshan, Kana M.
, p. 612 - 617 (2019)
Two cases of spontaneous evolution of monomers to linear polymers having novel cross-laminated topology are reported. We synthesized two peptide monomers N3-Gly-Gly-NH-CH2-CCH and N3-Gly-Gly-Gly-CH2-CCH and solved their crystal structures by single-crystal X-ray diffraction. They adopt H-bonded crisscrossed layered packing in their crystals such that: (a) the monomers are aligned head-to-tail in 1D-chain-like arrays and parallel arrangement of such arrays forms a layer; (b) the proximally placed azide and alkyne motifs are in an orientation apt for their regiospecific cycloaddition; (c) each monomer having x peptide bonds is H-bonded with 2x monomers disposed in intersecting arrangement, which pre-organize 1D-chain-like arrays in adjacent layers in perpendicular orientation. These crystals underwent spontaneous single-crystal-to-single-crystal (SCSC) polymerization via azide–alkyne cycloaddition reaction to form triazolyl-polyglycines, at room temperature. The crisscrossed arrangement of monomers in adjacent layers ensured the formation of cross-laminated polymers.
Ciprofloxacin/Gatifloxacin-1,2,3-triazole-isatin Hybrids and Their In Vitro Anticancer Activity
Jiang, Dan,Zhang, Guifu
, p. 2966 - 2969 (2019)
Eleven novel ciprofloxacin/gatifloxacin-1,2,3-triazole-isatin hybrids (8a–k) were designed, synthesized, and screened for their in vitro anticancer activity in this paper. A significant part of the synthesized hybrids was active against A549, HepG2, and SF-268 cancer cell lines, whereas the parent drugs ciprofloxacin and gatifloxacin were devoid of activity. Among them, hybrid 8i (IC50: 78.1–90.7 μM) was found to be the most active against A549, HepG2, and SF-268 cancer cell lines, and it was comparable with or better than Vorinostat (IC50: 71.1 to >100 μM). Thus, these kind hybrids have potentiality for discovery of new anticancer candidates for clinical deployment in the control and eradication of cancers.
Site-Specific 64Cu Labeling of the Serine Protease, Active Site Inhibited Factor Seven Azide (FVIIai-N3), Using Copper Free Click Chemistry
Jeppesen, Troels E.,Kristensen, Lotte K.,Nielsen, Carsten H.,Petersen, Lars C.,Kristensen, Jesper B.,Behrens, Carsten,Madsen, Jacob,Kjaer, Andreas
, p. 117 - 125 (2018)
A method for site-specific radiolabeling of the serine protease active site inhibited factor seven (FVIIai) with 64Cu has been applied using a biorthogonal click reaction. FVIIai binds to tissue factor (TF), a trans-membrane protein involved in hemostasis, angiogenesis, proliferation, cell migration, and survival of cancer cells. First a single azide moiety was introduced in the active site of this 50 kDa protease. Then a NOTA moiety was introduced via a strain promoted azide-alkyne reaction and the corresponding conjugate was labeled with 64Cu. Binding to TF and the stability was evaluated in vitro. TF targeting capability of the radiolabeled conjugate was tested in vivo by positron emission tomography (PET) imaging in pancreatic human xenograft cancer mouse models with various TF expressions. The conjugate showed good stability (>91% at 16 h), an immunoreactivity of 93.5%, and a mean tumor uptake of 2.1 ± 0.2%ID/g at 15 h post injection. In conclusion, FVIIai was radiolabeled with 64Cu in single well-defined position of the protein. This method can be utilized to prepare conjugates from serine proteases with the label at a specific position.
Stereoselective and Catalytic Synthesis of anti-β-Alkoxy-α-azido Carboxylic Derivatives
Fernández-Valparis, Javier,Romea, Pedro,Urpí, Fèlix,Font-Bardia, Mercè
, p. 6400 - 6403 (2017)
Direct addition of a chiral N-azidoacetyl thiazolidinethione to a variety of dialkyl acetals catalyzed by a commercially available and structurally simple nickel(II) complex gives access in good yields and a highly stereocontrolled manner to anti-β-alkoxy-α-azido carboxylic derivatives which, in turn, can be easily converted into a wide array of enantiomerically pure compounds.
Click strategy using disodium salts of amino acids improves the water solubility of plinabulin and KPU-300
Yakushiji, Fumika,Muguruma, Kyohei,Hayashi, Yoshiki,Shirasaka, Takuya,Kawamata, Ryosuke,Tanaka, Hironari,Yoshiwaka, Yushi,Taguchi, Akihiro,Takayama, Kentaro,Hayashi, Yoshio
, p. 3623 - 3630 (2017)
Plinabulin and KPU-300 are promising anti-microtubule agents; however, the low water solubility of these compounds (0.1?μg/mL) has limited their pharmaceutical advantages. Here, we developed five water-soluble derivatives of plinabulin and KPU-300 with a click strategy using disodium salts of amino acids. The mother skeleton, diketopiperazine (DKP), was transformed into a monolactim-type alkyne and a copper-catalyzed alkyne azide cycloaddition (CuAAC) combined azides that was derived from amino acids as a water-solubilizing moiety. The conversion of carboxyl groups into disodium salts greatly improved the water solubility by 0.8 million times compared to the solubility of the parent molecules. In addition, the α-amino acid side chains of the water-solubilizing moieties affected both the water solubility and the half-lives of the compounds during enzymatic hydrolysis. Our effort to develop a variety of water-soluble derivatives using the click strategy has revealed that the replaceable water-solubilizing moieties can alter molecular solubility and stability under enzymatic hydrolysis. With this flexibility, we are approaching to the in vivo study using water-soluble derivative.
Bioorthogonal chemistry for selective recognition, separation and killing bacteria over mammalian cells
Li, Zhenhua,Liu, Zhen,Chen, Zhaowei,Ju, Enguo,Li, Wei,Ren, Jinsong,Qu, Xiaogang
, p. 3482 - 3485 (2016)
By taking advantage of metabolic engineering and bioorthogonal click chemistry, we report a new strategy for selective recognition, separation and killing bacteria over mammalian cells.
Proteolysis Targeting Chimera (PROTAC) for Macrophage Migration Inhibitory Factor (MIF) Has Anti-Proliferative Activity in Lung Cancer Cells
Chen, Deng,Cool, Robbert H.,Dekker, Frank J.,Melgert, Barbro N.,Poelarends, Gerrit J.,Quax, Wim J.,Song, Shanshan,Xiao, Zhangping,van Merkerk, Ronald,van der Wouden, Petra E.
supporting information, p. 17514 - 17521 (2021/07/02)
Macrophage migration inhibitory factor (MIF) is involved in protein-protein interactions that play key roles in inflammation and cancer. Current strategies to develop small molecule modulators of MIF functions are mainly restricted to the MIF tautomerase active site. Here, we use this site to develop proteolysis targeting chimera (PROTAC) in order to eliminate MIF from its protein-protein interaction network. We report the first potent MIF-directed PROTAC, denoted MD13, which induced almost complete MIF degradation at low micromolar concentrations with a DC50 around 100 nM in A549 cells. MD13 suppresses the proliferation of A549 cells, which can be explained by deactivation of the MAPK pathway and subsequent induction of cell cycle arrest at the G2/M phase. MD13 also exhibits antiproliferative effect in a 3D tumor spheroid model. In conclusion, we describe the first MIF-directed PROTAC (MD13) as a research tool, which also demonstrates the potential of PROTACs in cancer therapy.
Discovery of triazolyl thalidomide derivatives as anti-fibrosis agents
Tang, Kai-Wei,Hsu, Wen-Li,Chen, Cheng-Ru,Tsai, Ming-Hsien,Yen, Chia-Jung,Tseng, Chih-Hua
, p. 3589 - 3599 (2021/03/03)
Fibrosis with excessive accumulation of extracellular matrix (ECM) often causes progressive organ dysfunction and results in many inflammatory and metabolic diseases, including systemic sclerosis, pulmonary fibrosis, advanced liver disease and advanced kidney disease. The store-operated calcium entry (SOCE) pathway and the related signaling pathway were both found to be the important routes for fibrogenesis. Our aim in this study was to discover novel compounds to inhibit fibrogenesis. A number of triazolyl thalidomide derivatives were synthesized and evaluated for their anti-fibrosis activities. Compounds 7b-e, 8c-d, 10a-b and 10e inhibited intracellular Ca2+ activation and showed no cytotoxicity. Among them, 6-{4-[(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl]-1H-1,2,3-triazol-1-yl}hexanoic acid (10e) with the most potent inhibitory effect was chosen for further examination. The results revealed that compound 10e, a SOCE inhibitor, reversed the migratory ability of TGF-β1-induced myofibroblasts, dedifferentiated myofibroblasts to fibroblasts due to cytoskeleton remodeling, and restrained myofibroblast activation by targeting Orai1 and TGF-β1/SMAD2/3 signaling pathways. The in silico study indicated that compound 10e, with the appropriate lipophilic carbon chain and carboxylic acid, showed a good drug-likeness model score. Conclusively, the SOCE inhibitor, compound 10e, is used as a promising lead compound for the development of a new treatment for fibrosis. This journal is
