- Structural and Activity Relationships of 6-Sulfonyl-8-Nitrobenzothiazinones as Antitubercular Agents
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The benzothiazinone (BTZ) scaffold compound PBTZ169 kills Mycobacterium tuberculosis by inhibiting the essential flavoenzyme DprE1, consequently blocking the synthesis of the cell wall component arabinans. While extraordinarily potent against M. tuberculosis with a minimum inhibitory concentration (MIC) less than 0.2 ng/mL, its low aqueous solubility and bioavailability issues need to be addressed. Here, we designed and synthesized a series of 6-methanesulfonyl substituted BTZ analogues; further exploration introduced five-member aromatic heterocycles as linkers to attach an aryl group as the side chain. Our work led to the discovery of a number of BTZ derived compounds with potent antitubercular activity. The optimized compounds 6 and 38 exhibited MIC 47 and 30 nM, respectively. Compared to PBTZ169, both compounds displayed increased aqueous solubility and higher stability in human liver microsomes. This study suggested that an alternative side-chain modification strategy could be implemented to improve the druglike properties of the BTZ-based compounds.
- Chiarelli, Laurent R.,Fan, Dongguang,Han, Quanquan,Lu, Yu,Qiao, Chunhua,Shi, Rui,Stelitano, Giovanni,Wang, Bin,Huszár, Stanislav,Miku?ová, Katarína,Savková, Karin
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supporting information
p. 14526 - 14539
(2021/10/26)
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- Discovery of new tranylcypromine derivatives as highly potent LSD1 inhibitors
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Tranylcypromine (TCP)-based structural modifications lead to the discovery of new LSD1 inhibitors, of which compounds 26b and 29b effectively inhibit LSD1 with the IC50 values of 17 and 11 nM, respectively and also show good selectivity over MAO-B. Mechanistic studies showed that compound 29b concentration-dependently induced H3K4me1/2 accumulation in LSD1 overexpressed MGC-803 cells and also inhibited metastasis of MGC-803 cells. Collectively, both compounds could be promising lead compounds for further investigation.
- Huang, Ming-Jie,Guo, Jia-Wen,Fu, Yun-Dong,You, Ya-Zhen,Xu, Wen-Yu,Song, Ting-Yu,Li, Ran,Chen, Zi-Tong,Huang, Li-Hua,Liu, Hong-Min
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supporting information
(2021/04/12)
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- A general procedure for carbon isotope labeling of linear urea derivatives with carbon dioxide
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Carbon isotope labeling is a traceless technology, which allows tracking the fate of organic compounds either in the environment or in living organisms. This article reports on a general approach to label urea derivatives with all carbon isotopes, including14C and11C, based on a Staudinger aza-Wittig sequence. It provides access to all aliphatic/aromatic urea combinations.
- Babin, Victor,Sallustrau, Antoine,Loreau, Olivier,Caillé, Fabien,Goudet, Amélie,Cahuzac, Hélo?se,Del Vecchio, Antonio,Taran, Frédéric,Audisio, Davide
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supporting information
p. 6680 - 6683
(2021/07/12)
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- Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer
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Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97?μM and 6.76 ± 0.25?μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.
- Li, Qingjiao,Liu, Yulin,Mao, Longfei,Peng, Lizeng,Xie, Luoyijun,Yang, Jianxue,Ye, Jiahui,Yuan, Miaomiao,Zhang, Rongjun
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- Cycloaddition Reactions of Azides and Electron-Deficient Alkenes in Deep Eutectic Solvents: Pyrazolines, Aziridines and Other Surprises
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The reaction of organic azides and electron-deficient alkenes was investigated in a deep eutectic solvents. A series of highly substituted 2-pyrazolines was successfully isolated and their formation rationalised by DFT calculations. The critical effect of substitution was also explored; even relatively small changes in the cycloaddition partners led to completely different reaction outcomes and triazolines, triazoles or enaminones can be formed as major products depending on the alkene employed. (Figure presented.).
- Casarrubios, Luis,Díez-González, Silvia,Lachhani, Kushal,Pimpasri, Chaleena,Rzepa, Henry S.,Sebest, Filip,White, Andrew J. P.
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supporting information
(2020/05/19)
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- New potent STS inhibitors based on fluorinated 4-(1-phenyl-1H-[1,2,3]triazol-4-yl)-phenyl sulfamates
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A series of fluorinated analogs based on the frameworks of 4-(1-phenyl-1H-[1,2,3]triazol-4-yl)-phenyl sulfamates have been synthesized as steroid sulfatase (STS) inhibitors. The design of chemical structures of new potential STS inhibitors was supported by molecular docking techniques to identify potential interactions between inhibitors and amino acid residues located in the STS active site. The STS inhibitory potency was evaluated on STS isolated from human placenta. We found that compounds substituted with fluorine atom at the meta position demonstrated the highest inhibitory effects in enzymatic STS assay. The most active analog 12e–inhibited STS enzyme with the IC50 value of 36 nM.
- Da?ko, Mateusz,Demkowicz, Sebastian,Rachon, Janusz,Biernacki, Karol,Aszyk, Justyna,Kozak, Witold,Mas?yk, Maciej,Kubiński, Konrad
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p. 1037 - 1044
(2019/12/03)
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- Synthesis and spectral properties of 6′-triazolyl-dihydroxanthene-hemicyanine fused near-infrared dyes
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We describe the synthesis of a range of 6′-triazolyl-dihydroxanthene-hemicyanine (DHX-hemicyanine) fused dyes through an effective copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click"reaction, with the aim of providing molecular diversity and evaluating the spectral properties of these near-infrared (NIR)-active materials. This was implemented by reacting 15 different aliphatic and aromatic azides with a terminal alkynyl-based DHX-hemicyanine hybrid scaffold prepared in four steps and 35% overall yield from 4-bromosalicylaldehyde. The resulting triazole derivatives have been fully characterized and their optical properties determined both in organic solvents and under simulated physiological conditions (phosphate buffered saline containing 5% of bovine serum albumin protein). This systematic study is a first important step towards the development of NIR-I fluorogenic "click-on"dyes or related photoactive agents for light-based diagnostic and/or therapeutic applications.
- Gu, Lingyue,Renault, Kévin,Romieu, Anthony,Richard, Jean-Alexandre,Srinivasan, Rajavel
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supporting information
p. 12208 - 12215
(2020/07/30)
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- Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity
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Gankyrin is an oncoprotein overexpressed in numerous cancer types and appears to play a key role in regulating cell proliferation, cell growth, and cell migration. These roles are largely due to gankyrin's protein-protein interaction with the 26S proteaso
- Almasri, Joseph,D'Souza, Amber,Dukhande, Vikas V.,Farrales, Pamela,Gnanmony, Manu,Gupta, Vivek,Juang, Daniel,Kabir, Abbas,Kanabar, Dipti,Muth, Aaron,Shukla, Snehal,Torrents, Nicolas
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supporting information
(2020/07/10)
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- Synthesis and Antitrypanosomal Activity of 1,4-Disubstituted Triazole Compounds Based on a 2-Nitroimidazole Scaffold: a Structure-Activity Relationship Study
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Chagas disease affects 6–8 million people worldwide, remaining a public health concern. Toxicity, several adverse effects and inefficiency in the chronic stage of the disease are the major challenges regarding the available treatment protocols. This work involved the synthesis of twenty-two 1,4-disubstituted-1,2,3-triazole analogues of benznidazole (BZN), by using a click chemistry strategy. Analogues were obtained in moderate to good yields (40-97 %). Antitrypanosomal activity was evaluated against the amastigote forms of Trypanosoma cruzi. Compound 8 a (4-(2-nitro-1H-imidazol-1-yl)methyl)-1-phenyl-1H-1,2,3-triazole) without substituents on phenyl ring showed similar biological activity to BZN (IC50=3.0 μM, SI>65.3), with an IC50=3.1 μM and SI>64.5. Compound 8 o (3,4-di-OCH3?Ph) with IC50 = 0.65 μM was five-fold more active than BZN, and showed an excellent selectivity index (SI>307.7). Compound 8 v (3-NO2, 4-CH3?Ph) with IC50=1.2 μM and relevant SI>166.7, also exhibited higher activity than BZN. SAR analysis exhibited a pattern regarding antitrypanosomal activity relative to BZN, in compounds with electron-withdrawing groups (Hammett σ+) at position 3, and electron-donating groups (Hammett σ-) at position 4, as observed in 8 o and 8 v. Further research might explore in vivo antitrypanosomal activity of promising analogues 8 a, 8 o, and 8 v. Overall, this study indicates that approaches such as the bioisosteric replacement of amide group by 1,2,3-triazole ring, the use of click chemistry as a synthesis strategy, and design tools like Craig-plot and Topliss tree are promising alternatives to drug discovery.
- Assun??o, Elvis L. F.,Carvalho, Diego B.,das Neves, Amarith R.,Kawasoko Shiguemotto, Cristiane Y.,Portapilla, Gisele B.,de Albuquerque, Sergio,Baroni, Adriano C. M.
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p. 2019 - 2028
(2020/09/21)
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- Baicalein triazole prevents respiratory tract infection by RSV through suppression of oxidative damage
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Baicalein, an isolate of secutellaria baicalensis is known for its anti-inflammatory activity. In the present study, 12-triazole derivatives of baicalein were synthesized and evaluated against RSV infected BEAS-2B cells in vitro and in mice model in vivo.
- Zhang, Cuicui,Li, Na,Niu, Fang
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p. 227 - 233
(2019/04/17)
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- Design, synthesis, and biological evaluation of 4-((6,7-dimethoxyquinoline-4-yl)oxy)aniline derivatives as FLT3 inhibitors for the treatment of acute myeloid leukemia
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FMS-like tyrosine kinase 3 (FLT3) was an important therapeutic target in acute myeloid leukemia (AML). We synthesized two series of 4-((6,7-dimethoxyquinoline-4-yl)oxy)aniline derivatives possessing the semicarbazide moiety and 2,2,2-trifluoro-N,N′-dimeth
- Xu, Qiaoling,Dai, Baozhu,Li, Zhiwei,Xu, Le,Yang, Di,Gong, Ping,Hou, Yunlei,Liu, Yajing
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supporting information
(2019/08/27)
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- Design, synthesis and biological evaluation of novel 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole triazole derivatives as potent TRPV1 antagonists
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Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (6g), a potent TRPV1 antagonist. In vitro, using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC50 = 0.075 μM) and only partially blocked acid activation of TRPV1. In vivo, 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs.
- Li, Jinyu,Nie, Cunbin,Qiao, Yue,Hu, Jing,Li, Qifei,Wang, Qiang,Pu, Xiaohui,Yan, Lin,Qian, Hai
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p. 433 - 445
(2019/06/18)
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- Multifunctional Mono-Triazole Derivatives Inhibit Aβ42 Aggregation and Cu2+-Mediated Aβ42 Aggregation and Protect against Aβ42-Induced Cytotoxicity
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Amyloid beta (Aβ) peptide aggregation is considered as one of the key hallmarks of Alzheimer's disease (AD). Moreover, Aβ peptide aggregation increases considerably in the presence of metal ions and triggers the generation of reactive oxygen species (ROS)
- Kaur, Amandeep,Narang, Simranjeet Singh,Kaur, Anupamjeet,Mann, Sukhmani,Priyadarshi, Nitesh,Goyal, Bhupesh,Singhal, Nitin Kumar,Goyal, Deepti
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p. 1824 - 1839
(2019/09/30)
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- Design, synthesis,: In silico docking studies and biological evaluation of novel quinoxaline-hydrazide hydrazone-1,2,3-triazole hybrids as α-glucosidase inhibitors and antioxidants
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A new series of quinoxaline-hydrazidehydrazone-1,2,3-triazole hybrids, 14a-j, 15a-j and 16a-e, was designed, synthesized and screened for in vitro α-glucosidase and antioxidant activities. For the synthesis of the target compounds, quinoxaline hydrazides were condensed with benzaldehyde triazoles in the presence of AcOH (cat) in ethanol. The key step in the preparation of compounds 8a-j was the Cu(i)-catalyzed [3+2] cycloaddition reaction (CuAAC) with appropriate alkynes (6, 7) and azides, and 13a-j were prepared from simple aldehydes utilizing the same click reaction as the final step. Quinoxaline hydrazides (3, 3a) were synthesized from o-phenylenediamine and pyruvic acid via three-step reactions comprising cyclization, alkylation and hydrazidation. Among these hybrids, 14a (IC50 = 21.92 μg mL-1), 14b (IC50 = 22.32 μg mL-1), 14c (IC50 = 23.58 μg mL-1) and 15a (IC50 = 24.50 μg mL-1) showed good α-glucosidase inhibition compared with the standard acarbose (IC50 = 22.32 μg mL-1). Further, the scavenging abilities of the synthesized compounds as antioxidants were studied using the DPPH, H2O2, and NO methods; as per the obtained results, compounds 14a, 14b, 14c and 15a displayed good antioxidant activity. Docking studies of the active compounds and acarbose as a standard with α-glucosidase (PDB ID: 2ZEO) were performed to determine the molecular interactions between the inhibitors and the active site of the enzyme. Better binding energies of the active compounds than of the standard acarbose were observed. Therefore, our new hybrid molecules may be useful for further optimization in developing new lead molecules with both α-glucosidase inhibition and antioxidant activities.
- Settypalli, Triloknadh,Chunduri, Venkata Rao,Maddineni, Aruna Kumari,Begari, Nagaraju,Allagadda, Rajasekhar,Kotha, Peddanna,Chippada, Appa Rao
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p. 15435 - 15452
(2019/10/08)
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- Design, synthesis and antibacterial evaluation of novel 15-membered 11a-azahomoclarithromycin derivatives with the 1, 2, 3-triazole side chain
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Macrolides are widely prescribed in clinic to treat various respiratory tract infections. However, due to their inappropriate use, the prevalence of macrolide-resistant strains among clinical isolates has become a concern for public health. Therefore, nov
- Qin, Yinhui,Teng, Yuetai,Ma, Ruixin,Bi, Fangchao,Liu, Zhiyang,Zhang, Panpan,Ma, Shutao
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p. 321 - 339
(2019/07/18)
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- Synthesis and In Vitro Evaluation of 1,2,3-triazole-4-chloromethylcoumarins with Antioxidant Activity
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Background: Coumarins are secondary plant metabolites typically found in the species of Asteraceae, Rutaceae and Umbeliferae families which demonstrate several pharmacological properties, including antioxidant activity. As antioxidants, coumarins are know
- Alves, Anna Carolina Schneider,Munhoz, Thaís,Soares, Fabiana Gomes Nascimento,Rockenbach, Liliana,Gauer, Bruna,Kawano, Daniel Fábio,von Poser, Gilsane Lino,Garcia, Solange Cristina,Eifler-Lima, Vera Lucia
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p. 700 - 705
(2018/06/27)
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- Thermal azide-Alkene cycloaddition reactions: straightforward multi-gram access to Δ2-1,2,3-Triazolines in deep eutectic solvents
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The multi-gram synthesis of a wide range of 1,2,3-Triazolines via azide-Alkene cycloaddition reactions in a Deep Eutectic Solvent (DES) is reported. The role of DES in this transformation as well as the origin of the full product distribution was studied with an experimental/computational-DFT approach.
- Sebest, Filip,Casarrubios, Luis,Rzepa, Henry S.,White, Andrew J. P.,Díez-González, Silvia
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supporting information
p. 4023 - 4035
(2018/09/11)
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- Synthesis, docking and ADME prediction of novel 1,2,3-triazole-tethered coumarin derivatives as potential neuroprotective agents
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In an attempt to find potential neuroprotective agents, a series of novel 3-(1-((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl) methoxyimino) ethyl)-2H-chromen-2-one derivatives 6a–j were synthesized by using “click reaction” and evaluated for their in vit
- Kumari, Maddineni Aruna,Rao, Chunduri Venkata,Triloknadh, Settypalli,Harikrishna, Nallapaneni,Venkataramaiah, Chintha,Rajendra, Wudayagiri,Trinath, Daggupati,Suneetha, Yeguvapalli
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p. 1989 - 2008
(2017/12/04)
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- Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan
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Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving chemoresistance in cancers such as renal cell carcinoma (RCC). Using a cell-based luciferase reporter assay to screen small molecules, we identified a novel inhibitor of miR-21 function. Following structure-activity relationship studies, an optimized lead compound demonstrated cytotoxicity in several cancer cell lines. In a chemoresistant-RCC cell line, inhibition of miR-21 via small molecule treatment rescued the expression of tumor-suppressor proteins and sensitized cells to topotecan-induced apoptosis. This resulted in a >10-fold improvement in topotecan activity in cell viability and clonogenic assays. Overall, this work reports a novel small molecule inhibitor for perturbing miR-21 function and demonstrates an approach to enhancing the potency of chemotherapeutics specifically for cancers derived from oncomir addiction.
- Naro, Yuta,Ankenbruck, Nicholas,Thomas, Meryl,Tivon, Yaniv,Connelly, Colleen M.,Gardner, Laura,Deiters, Alexander
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p. 5900 - 5909
(2018/08/04)
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- Synthesis and antimicrobial activity of 4-substituted 1,2,3-triazole-coumarin derivatives
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A new series of coumarin-1,2,3-triazole conjugates with varied alkyl, phenyl and heterocycle moieties at C-4 of the triazole nucleus were synthesized using a copper(I)-catalysed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O-propargylated coumarin (3) or N-propargylated coumarin (6) with alkyl or aryl azides. Based on their minimal inhibitory concentrations (MICs) against selected microorganisms, six out of twenty-six compounds showed significant antibacterial activity towards Enterococcus faecalis (MIC = 12.5–50 μg/mL). Moreover, the synthesized triazoles show relatively low toxicity against human erythrocytes.
- López-Rojas, Priscila,Janeczko, Monika,Kubiński, Konrad,Amesty, ángel,Mas?yk, Maciej,Estévez-Braun, Ana
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- Design, synthesis, molecular-docking and antimycobacterial evaluation of some novel 1,2,3-triazolyl xanthenones
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As part of an ongoing effort to develop new antitubercular and antimicrobial agents, a series of substituted xanthenone derivatives (7a-p) were synthesized. Xanthenone derivatives (7a-p) were prepared via a one-pot three-component thermal cyclization reac
- Goud, Gudikadi Linga,Ramesh, Seela,Ashok, Dongamanti,Reddy, Vummenthala Prabhakar,Yogeeswari, Perumal,Sriram, Dharmarajan,Saikrishna, Balabadra,Manga, Vijjulatha
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p. 559 - 570
(2017/03/30)
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- Design, combinatorial synthesis and biological evaluations of novel 3-amino-1'-((1-aryl-1H-1,2,3-triazol-5-yl)methyl)-2'-oxospiro[benzo[a] pyrano[2,3-c]phenazine-1,3'-indoline]-2-carbonitrile antitumor hybrid molecules
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A combinatorial chemical library of fifty-nine novel 3-amino-1'-((1-aryl-1H-1,2,3-triazol-5-yl)methyl)-2'-oxospiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline]-2-carbonitrile, designed as hybrid molecules of phenazine, pyran, indole and 1,2,3-triazole pharmacophores, were constructed in this study. Cytotoxic evaluation indicated that some compounds exhibited moderate cytotoxicity against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro, in which compound 36 was found to have best antiproliferative activity against the A549 cancer cell line with IC50 value of 5.4 μM. All compounds had low or no effect against L02 and HUVEC non-cancer cell lines. Compound 36 was further confirmed to mainly locate mitochondria in A549 cancer cells via laser-scanning confocal microscopy. Moreover, compound 36 was proved to increase ROS production and induce cell cycle arrest in S phase. Western blot analysis illustrated Bax/Bcl-2 ratio was increased at dose-dependent manner, and both cleaved caspase-3 and cleaved caspase-9 was enhanced by treated with compound 36. All the above evidences in vitro indicated that compound 36 might induce the apoptosis of A549 cancer cells via a mitochondria-dependent pathway.
- Lu, Yuanyuan,Wang, Linlin,Wang, Xiaobing,Xi, Tao,Liao, Jianmin,Wang, Zhixiang,Jiang, Feng
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p. 125 - 141
(2017/04/26)
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- General Method for the Synthesis of 1,4-Disubstituted 5-Halo-1,2,3-triazoles
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A general method for the synthesis of 1,4-disubstituted 5-halo-1,2,3-triazoles has been developed. The one-pot two-step process consists of a CuAAC reaction of a copper(I) acetylide with an organic azide catalyzed by (aNHC)CuCl, followed by halogenation with N-chlorosuccinimide, N-bromosuccinimide, or I2.
- Gribanov, Pavel S.,Topchiy, Maxim A.,Karsakova, Iuliia V.,Chesnokov, Gleb A.,Smirnov, Alexander Yu.,Minaeva, Lidiya I.,Asachenko, Andrey F.,Nechaev, Mikhail S.
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supporting information
p. 5225 - 5230
(2017/09/29)
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- An unprecedentedly simple method of synthesis of aryl azides and 3-hydroxytriazenes
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Fischer's approach towards the synthesis of aryl azides and triazinoles from diazonium salts and hydroxylammonium chloride (phenylhydraxylamine) was reinvestigated and optimized. The new methodology enables the preparation of aryl azides and triazinoles in high yields in water at room temperature. The procedure is very simple, robust, easily scalable, reproducible, and "green".
- Gribanov, Pavel S.,Topchiy, Maxim A.,Golenko, Yulia D.,Lichtenstein, Yana I.,Eshtukov, Artur V.,Terekhov, Vladimir E.,Asachenko, Andrey F.,Nechaev, Mikhail S.
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supporting information
p. 5984 - 5988
(2018/06/06)
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- A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer
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A range of 1,4-substituted 2-pyridyl-N-phenyl triazoles were synthesised and evaluated for their antiproliferative properties against lymph node cancer of the prostate (LNCaP) and bone metastasis of prostate cancer (PC-3) cells. Excellent-to-low IC50 values were determined (5.6-250 μM), and a representative group of 4 ligands were then complexed to iridium(III) giving highly luminescent species. Reevaluation of these compounds against both cell lines was then undertaken and improved potency (up to 72-fold) was observed, giving IC50 values of 0.36-11 μM for LNCaP and 0.85-5.9 μM for PC-3. Preliminary screens for in vivo toxicity were conducted using a zebrafish model showing a wide range of induced toxicity depending of the compound evaluated. Apoptosis and Caspase-3 levels were also determined and showed no statistical difference between some of the treated specimens and the controls. This study may identify novel therapeutic agents for advanced stage of prostate cancer in humans.
- Hockey, Samantha C.,Barbante, Gregory J.,Francis, Paul S.,Altimari, Jarrad M.,Yoganantharajah, Prusothman,Gibert, Yann,Henderson, Luke C.
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p. 305 - 313
(2016/01/28)
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- Synthesis of novel 1,2,3-triazole-containing pyridinepyrazole amide derivatives based on one-pot click reaction and their evaluation for potent nematicidal activity against Meloidogyne incognita
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In order to find a novel, leading nematicide compound, a series of pyridinepyrazole amide derivatives containing 1,2,3-triazoles were synthesized via click chemistry in a one-pot reaction. Their structures were characterized by proton nuclear magnetic res
- Chen, Xiulei,Xiao, Youxin,Wang, Gaolei,Li, Zhong,Xu, Xiaoyong
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p. 5495 - 5508
(2016/06/01)
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- Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1-Nrf2 Protein-Protein Interaction
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The transcription factor Nrf2 regulates the expression of a large network of cytoprotective and metabolic enzymes and proteins. Compounds that directly and reversibly inhibit the interaction between Nrf2 and its main negative regulator Keap1 are potential pharmacological agents for a range of disease types including neurodegenerative conditions and cancer. We describe the development of a series of 1,4-diphenyl-1,2,3-triazole compounds that inhibit the Nrf2-Keap1 protein-protein interaction (PPI) in vitro and in live cells and up-regulate the expression of Nrf2-dependent gene products.
- Bertrand, Hélène C.,Schaap, Marjolein,Baird, Liam,Georgakopoulos, Nikolaos D.,Fowkes, Adrian,Thiollier, Clarisse,Kachi, Hiroko,Dinkova-Kostova, Albena T.,Wells, Geoff
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supporting information
p. 7186 - 7194
(2015/10/05)
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- Synthesis of novel 1-substituted triazole linked 1,2-benzothiazine 1,1-dioxido propenone derivatives as potent anti-inflammatory agents and inhibitors of monocyte-to-macrophage differentiation
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A series of novel 1-substituted-triazole linked 1,2-benzothiazine 1,1-dioxido propenone derivatives 8a-s & 12a-l were prepared from 1-substituted 1,2,3-triazol-4-aldehydes 6 & 11 with N-methyl-3-acetyl-4-hydroxybenzothiazine-1,1-dioxide 7 by condensation.
- Gannarapu, Malla Reddy,Vasamsetti, Sathish Babu,Punna, Nagender,Kotamraju, Srigiridhar,Banda, Narsaiah
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supporting information
p. 1494 - 1500
(2015/08/18)
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- Synthesis and insecticidal evaluation of novel phthalic diamides containing 1,2,3-triazoles via click reaction
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A series of novel phthalic diamide derivatives containing 1,2,3-triazole moiety were synthesized using one-pot click chemistry approach and characterized by 1H NMR and HRMS. The insecticidal activity against armyworm (Mythimna separata), Tetranychu scinnabarinus and cowpea aphid (Aphis craccivora) was evaluated. Compounds 4II-a and 4II-i showed 50% insecticidal activity against armyworm (Mythimna separata) at the concentration of 4 mg/L and one-third of the compounds had moderate activity against Tetranychus cinnabarinus at 500 mg/L. Copyright
- Chen, Yinbo,Xiao, Youxin,Shao, Xusheng,Xu, Xiaoyong,Li, Zhong
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p. 592 - 598
(2014/07/22)
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- 1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as orally bioavailable transcriptional function suppressors of Estrogen-related receptor α
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Estrogen-related receptor α is a potential candidate target for therapeutic treatment of breast cancer. We describe the discovery and structure-activity relationship study of a series of 1-phenyl-4-benzoyl-1H-1,2, 3-triazoles as novel suppressors of ERRα
- Xu, Shilin,Zhuang, Xiaoxi,Pan, Xiaofen,Zhang, Zhang,Duan, Lei,Liu, Yingxue,Zhang, Lianwen,Ren, Xiaomei,Ding, Ke
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p. 4631 - 4640
(2013/07/19)
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- Studies on synthesis of novel triazolalkyl tagged trifluoromethyl substituted pyrimidine derivatives and their evaluation for cytotoxic activity
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The 2-amino-6-trifluoromethyl-3H-pyrimidin-4-one 1 was propargylated to give two regioisomers 2, 3 in definite proportions. Both regioisomers 2 and 3 were independently reacted with alkyl, aryl or cycloalkyl substituted azides under Sharpless conditions a
- Nagender, Punna,Reddy, Gannarapu Malla,Kumar, Royya Naresh,Reddy, Anugu Chandrashekar,Velatooru, Loka Reddy,Pamanji, Rajesh,Rao, Janapala Venkateswara,Narsaiah, Banda
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p. 865 - 871
(2013/12/04)
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- Rhodium-catalyzed direct C-H amination of benzamides with aryl azides: A synthetic route to diarylamines
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No muss, no fuss: A rhodium-catalyzed direct intermolecular C-H amination of benzamides and ketoximes using aryl azides as the amine source has been developed. The reaction exhibits a broad substrate scope with excellent functional-group tolerance, requires no external oxidants, releases N 2 as the only by-product, and produces diarylamines in high yields. Copyright
- Ryu, Jaeyune,Shin, Kwangmin,Park, Sae Hume,Kim, Ji Young,Chang, Sukbok
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supporting information
p. 9904 - 9908
(2012/10/29)
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- 8-TRIAZOLYLXANTHINE DERIVATIVES, PROCESSES FOR THEIR PRODUCTION AND THEIR USE AS ADENOSINE RECEPTOR ANTAGONISTS
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The invention relates to derivatives of the general formulae (I) and (II) to processes for the production thereof, to pharmaceutical preparations containing said compounds and/or physiologically compatible salts or solvates or prodrugs which can be produced therefrom as well as to the pharmaceutical use of said compounds, the salts or solvates thereof as adenosine receptor antagonists, in particular for the treatment of neurodegenerative disorders, e.g. stroke, amylotrophic lateral sclerosis, dementia, Alzheimer's disease, Parkinson's disease, ischemia/reperfusion injury, inflammation, and/or neurological disorder. The blockade of adenosine receptors could also be useful for other indications regarding the metabolism, e.g. diabetic retinopathy, diabetes mellitus, hyperbaric oxygen - induced retinopathy and/or obesity. Applications could also be the treatment of allergic diseases and autoimmune diseases, including mast cell degranulation, asthma, bronchoconstriction, pulmonary fibrosis, inflammatory or obstructive airways disease and/or chronic obstructive pulmonary disease (COPD). In addition, they could be used to treat cancer. The diseases associated with adenosine receptors are also diabetes, diarrhea, inflammatory bowel disease and/or gastrointestinal tract disorders. Adenosine receptor antagonists could be effective for treating a hepatic disease or condition for reducing fat deposition in the liver or fibrosis of the liver. The use of compounds of general formulae I or II can be associated with many applications e.g., scleroderm arthritis, atherosclerosis, urticaria, myocardial infarction, myocardial reperfusion after ischemia, vasodilation, hypertension, hypersensitivity, myocardial ischemia, heart attack and/or retinopathy of prematurity.
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Page/Page column 37-38
(2012/06/30)
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