- 7-Aryl-triazolyl-substituted sulfocoumarins are potent, selective inhibitors of the tumor-associated carbonic anhydrase IX and XII
-
Sulfocoumarins behave as interesting inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Here, we report a new series of 7-substituted derivatives which were obtained by the click chemistry approach from 7-propargyloxy-sulfocoumarin and aryl azides incorporating halogens, hydroxy, methoxy and carboxyl moieties in their molecules. The new compounds were screened for the inhibition on four physiologically relevant human CA (hCA) isoforms, the cytosolic hCA I and II and the transmembrane tumor-associated hCA IX and XII. The new compounds did not inhibit the cytosolic isoforms but were low nanomolar inhibitors of the tumor-associated ones hCA IX and XII.
- Nocentini, Alessio,Ceruso, Mariangela,Carta, Fabrizio,Supuran, Claudiu T.
-
-
Read Online
- New potent steroid sulphatase inhibitors based on 6-(1-phenyl-1H-1,2,3-triazol-4-yl)naphthalen-2-yl sulphamate derivatives
-
In the present work, we report a new class of potent steroid sulphatase (STS) inhibitors based on 6-(1-phenyl-1H-1,2,3-triazol-4-yl)naphthalen-2-yl sulphamate derivatives. Within the set of new STS inhibitors, 6-(1-(1,2,3-trifluorophenyl)-1H-1,2,3-triazol
- Ciupak, Olga,Da?ko, Mateusz,Biernacki, Karol,Rachon, Janusz,Mas?yk, Maciej,Kubiński, Konrad,Martyna, Aleksandra,Demkowicz, Sebastian
-
-
Read Online
- Synthesis, antiproliferative, docking and DFT studies of benzimidazole derivatives as EGFR inhibitors
-
In the present work, new benzimidazole linked 1,2,3-triazole hybrids have been synthesized and screened for antiproliferative and EGFR kinase inhibitory activities.The structures of these hybrids were elucidated using IR, NMR, mass spectrometry and elemen
- Alam, Mohammad Mahboob,Alzahrani, Hessah Abdullah,Elhenawy, Ahmed A.,Malebari, Azizah M.,Nazreen, Syed
-
-
- Structural and Activity Relationships of 6-Sulfonyl-8-Nitrobenzothiazinones as Antitubercular Agents
-
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
-
supporting information
p. 14526 - 14539
(2021/10/26)
-
- A general procedure for carbon isotope labeling of linear urea derivatives with carbon dioxide
-
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
-
supporting information
p. 6680 - 6683
(2021/07/12)
-
- Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
-
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
- Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
-
supporting information
p. 4623 - 4661
(2021/05/07)
-
- Synthesis, antimicrobial evaluation, and in silico studies of quinoline—1H-1,2,3-triazole molecular hybrids
-
Abstract: Antimicrobial resistance has become a significant threat to global public health, thus precipitating an exigent need for new drugs with improved therapeutic efficacy. In this regard, molecular hybridization is deemed as a viable strategy to afford multi-target-based drug candidates. Herein, we report a library of quinoline—1H-1,2,3-triazole molecular hybrids synthesized via copper(I)-catalyzed azide-alkyne [3 + 2] dipolar cycloaddition reaction (CuAAC). Antimicrobial evaluation identified compound 16 as the most active hybrid in the library with a broad-spectrum antibacterial activity at an MIC80 value of 75.39?μM against methicillin-resistant S. aureus, E. coli, A. baumannii, and multidrug-resistant K. pneumoniae. The compound also showed interesting antifungal profile against C. albicans and C. neoformans at an MIC80 value of 37.69 and 2.36?μM, respectively, superior to fluconazole. In vitro toxicity profiling revealed non-hemolytic activity against human red blood cells (hRBC) but partial cytotoxicity to human embryonic kidney cells (HEK293). Additionally, in silico studies predicted excellent drug-like properties and the importance of triazole ring in stabilizing the complexation with target proteins. Overall, these results present compound 16 as a promising scaffold on which other molecules can be modeled to deliver new antimicrobial agents with improved potency. Graphic abstract: [Figure not available: see fulltext.].
- Awolade, Paul,Cele, Nosipho,Kerru, Nagaraju,Singh, Parvesh
-
p. 2201 - 2218
(2020/06/17)
-
- 2-((1-Phenyl-1H-1,2,3-triazol-4-yl)methyl)-2-azabicyclo[3.2.1]octan-3-one derivatives: Simplification and modification of aconitine scaffold for the discovery of novel anticancer agents
-
The molecular chaperone heat shock protein 90 (Hsp90) is a promising target for cancer therapy. Natural product aconitine is a potential Hsp90 inhibitor reported in our previous work. In this study, we designed and synthesized a series of 2-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)-2-azabicyclo[3.2.1]octan-3-one derivatives as potent Hsp90 inhibitors by simplifying and modifying aconitine scaffold. Among these compounds, 14t exhibited an excellent antiproliferative activity against LoVo cells with an IC50 value of 0.02 μM and a significant Hsp90α inhibitory activity with an IC50 value of 0.71 nM. Molecular docking studies provided a rational binding model of 14t in complex with Hsp90α. The following cell cycle and apoptosis assays revealed that compound 14t could arrest cell cycle at G1/S phase and induce cell apoptosis via up-regulation of bax and cleaved-caspase 3 protein expressions while inhibiting the expressions of bcl-2. Moreover, 14t could inhibit cell migration in LoVo and SW620 cell lines. Consistent with in vitro results, 14t significantly repressed tumor growth in the SW620 xenograft mouse model.
- Zhang, Yi,Zhang, Ting-jian,Li, Xin-yang,Liang, Jing-wei,Tu, Shun,Xu, Hai-li,Xue, Wen-han,Qian, Xin-hua,Zhang, Zhen-hao,Zhang, Xu,Meng, Fan-hao
-
-
- Synthesis, Characterization, and Cytotoxic Evaluation of New Triazole Derivatives of Osthol
-
Abstract: Osthol [7-methoxy-8-(3-methylbut-2-en-1-yl)chromen-2-one] isolated fromPrangos pabularia was used as a startingmaterial for the synthesis of its various derivatives via modifications of thelactone ring. The resulting compounds were fully charact
- Banday, J. A.,Chisti, H. N.,Rather, Z. K.
-
p. 986 - 993
(2021/07/22)
-
- Primary discovery of 1-aryl-5-substituted-1H-1,2,3-triazole-4-carboxamides as promising antimicrobial agents
-
Three series of novel 1H-1,2,3-triazole-4-carboxamides: 1-aryl-5-alkyl/aryl-1H-1,2,3-triazole-4-carboxamides, 1-aryl-5-amino-1H-1,2,3-triazole-4-carboxamides and 1,2,3-triazolo[1,5-a]quinazoline-3-carboxamides were synthesized via base-mediated click azide reactions. Compounds were evaluated for their antimicrobial activities against primary pathogens: Gram-positive and Gram-negative bacterial strains Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, as well as fungal strain Cryptococcus neoformans var. grubii and Candida albicans. Compounds exhibiting moderate to good activities were selected for SAR analysis. Several 5-methyl-1H-1,2,3-triazole-4-carboxamides 4d, 4l, 4r, showed potent antibacterial effect against S. aureus. On the contrary, 5-amino-1H-1,2,3-triazole-4-carboxamide 8b and [1,2,3]triazolo[1,5-a]quinazoline-3-carboxamide 9a were active against pathogenic yeast C. albicans. Thus, compound 4l under 1 μM demonstrated 50% growth inhibition against S. aureus. At the same concentration, the compound 9a killed approx. 40% of C. albicans cells. In general, these compounds demonstrated selective action and no significant impact on the viability of human keratinocytes of HaCaT line.
- Finiuk, Nataliya,Klyuchivska, Olha,Manko, Nazar,Matiychuk, Vasyl,Obushak, Mykola,Pokhodylo, Nazariy,Stoika, Rostyslav
-
-
- Naproxen based 1,3,4-oxadiazole derivatives as EGFR inhibitors: Design, synthesis, anticancer, and computational studies
-
A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hy-brids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15) was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 μg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 μg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.
- Alam, Mohammad Mahboob,Alfaifi, Mohammad Y.,Alfaifi, Sulaiman Y. M.,Almalki, Abdulraheem S. A.,Alsenani, Nawaf I.,Alsharif, Meshari A.,Elbehairi, Serag Eldin I.,Elhenawy, Ahmed A.,Malebari, Azizah M.,Nazreen, Syed
-
-
- Synthesis and biological evaluation of 1,2,3-triazole tethered thymol-1,3,4-oxadiazole derivatives as anticancer and antimicrobial agents
-
A library of 1,2,3-triazole-incorporated thymol-1,3,4-oxadiazole derivatives (6–18) hasbeen synthesized and tested for anticancer and antimicrobial activities. Compounds 7, 8, 9, 10, and 11 exhibited significant antiproliferative activity. Among these act
- Ahmad, Abrar,Alam, Mohammad Mahboob,Alfaifi, Sulaiman Y. M.,Alghamdi, Abdullah A. A.,Ali, Nada M.,Almalki, Abdulraheem S. A.,Alsharif, Meshari A.,Elhenawy, Ahmed A.,Malebari, Azizah M.,Nazreen, Syed
-
-
- Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer
-
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
-
-
- Design, synthesis and biological evaluation of homoerythrina alkaloid derivatives bearing a triazole moiety as PARP-1 inhibitors and as potential antitumor drugs
-
A series of homoerythrina alkaloid derivatives containing a 1,2,3-triazole moiety as PARP-1 inhibitors were designed and synthesized. And their anti-proliferative activity was further evaluated. Compound 10n had excellent activity to inhibit proliferation of A549 cells (IC50 = 1.89 μM), which was higher than harringtonine (IC50 = 10.55 μM), pemetrexed (IC50 = 3.39 μM), and rucaparib (IC50 = 4.91 μM). Furthermore, the selectivity index of compound 10n was higher than rucaparib and pemetrexed for lung cancer cells. Flow cytometry analysis showed that compound 10n significantly arrested the cell cycle in the S phase, then induced apoptosis of A549 cells (apoptosis rate is 46%), which effectively inhibited cell proliferation. Simultaneously, western blot analysis revealed that compound 10n could prevent the biosynthesis of PAR. Further analysis results revealed that compound 10n could inhibit the expression of cyclin A, down-regulate the expression of bcl-2/bax, activate caspase-3, and ultimately induce apoptosis of A549 cells. All the results indicated that compound 10n had potential research value as a novel PARP-1 inhibitor in antitumor, and it provided a new reference for further development of PARP-1 inhibitors.
- Li, Shuai,Li, Xin-yang,Zhang, Ting-jian,Kamara, Mohamed Olounfeh,Liang, Jing-wei,Zhu, Ju,Meng, Fan-hao
-
-
- Design, synthesis and biological evaluation of erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors
-
Inhibitors of poly (ADP-ribose) polymerase-1 (PARP-1) have shown to be promising in clinical trials against cancer, and many researchers are interested in the development of new PARP-1 inhibitors. Herein, we designed and synthesized 44 novel erythrina derivatives bearing a 1,2,3-triazole moiety as PARP-1 inhibitors. MTT assay results indicated that compound 10b had the most potent anti-proliferative activity against A549 cells among five cancer cells. The enzyme inhibitory activity in vitro of compound 10b was also significantly better than rucaparib. Furthermore, the selectivity index of compound 10b was higher than rucaparib for lung cancer cells. Flow cytometry analysis showed that compound 10b induced apoptosis of A549 cells by the mitochondrial pathway. Western blot analysis indicated that compound 10b was able to inhibit the biosynthesis of PAR effectively, and it was more potent than rucaparib. Also, compound 10b was able to up-regulate the ratio of bax/bcl-2, activate caspase-3, and ultimately induced apoptosis of A549 cells. The combined results revealed that the discovery of novel non-amide based PARP-1 inhibitors have great research significance and provide a better choice for the future development of drugs.
- Li, Shuai,Li, Xin-yang,Meng, Fan-hao,Qian, Xin-hua,Xue, Wen-han,Zhang, Ting-jian,Zhu, Ju
-
supporting information
(2020/01/21)
-
- Optimizing the aryl-triazole of cjoc42 for enhanced gankyrin binding and anti-cancer activity
-
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
-
supporting information
(2020/07/10)
-
- Design, synthesis and anti-platelet aggregation activity study of ginkgolide-1,2,3-triazole derivatives
-
Ginkgolides are the major active component of Ginkgo biloba for inhibition of platelet activating factor receptor. An azide-alkyne Huisgen cycloaddition reaction was used to introduce a triazole nucleus into the target ginkgolide molecules. A series of ginkgolide-1,2,3-triazole conjugates with varied functional groups including benzyl, phenyl and heterocycle moieties was thus synthesized. Many of the designed derivatives showed potent antiplatelet aggregation activities with IC50 values of 5~21 nM.
- Cui, Jian,Hu, Lean,Shi, Wei,Cui, Guozhen,Zhang, Xumu,Zhang, Qing-Wen
-
-
- Leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry. Part II
-
Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC50 value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.
- Cao, Jiangying,Zang, Jie,Kong, Xiujie,Zhao, Chunlong,Chen, Ting,Ran, Yingying,Dong, Hang,Xu, Wenfang,Zhang, Yingjie
-
p. 978 - 990
(2019/02/09)
-
- Synthesis and discovery of asiatic acid based 1,2,3-triazole derivatives as antitumor agents blocking NF-κB activation and cell migration
-
A series of asiatic acid (AA) based 1,2,3-triazole derivatives were designed, synthesized and subjected to a cell-based NF-κB inhibition screening assay. Among the tested compounds, compound 6k displayed impressive NF-κB inhibitory activity with an ICsub
- Huang, Ri-Zhen,Liang, Gui-Bin,Li, Mei-Shan,Fang, Yi-Lin,Zhao, Shi-Feng,Zhou, Mei-Mei,Liao, Zhi-Xin,Sun, Jing,Wang, Heng-Shan
-
p. 584 - 597
(2019/04/30)
-
- Thiophenol-formaldehyde triazole causes apoptosis induction in ovary cancer cells and prevents tumor growth formation in mice model
-
In the present study a library of thiophenol-formaldehyde-triazole (TFT) derivatives was synthesized and screened against CAOV3, CAOV4 and ES-2 ovary cancer cell lines. Initial screening revealed that five-compounds 5a, 5b, 5j, 5h and 5i inhibited the viability of tested cell lines. Analysis of apoptosis revealed that increase in compound 5a (most active) concentration from 0.25 to 2.0 μM enhanced apoptotic cell proportion. Transwell assay showed reduction in invasive potential of CAOV3 cells on treatment with compound 5a. In wound healing assay increasing the concentration of compound 5a from 0.5 to 2.0 μM caused a significant (P 0.05) decrease in the migration potential. Western blotting showed that compound 5a treatment markedly decreased the level of matrix metalloproteinase (MMP)-2 and ?9 in CAOV3 cells. Treatment of CAOV3 cells with compound 5a caused a marked decrease in Focal Adhesion Kinase (FAK) activation. Tumor growth was inhibited in the compound 5a treated mice markedly than those of untreated group. The tumor metastasis to liver, intestine, spleen and peritoneal cavity was markedly decreased in mice treated with 10 mg/kg dose of compound 5a. Examination of Von Willebrand factor (vWF) expression in liver, intestinal and pulmonary lesions showed a marked decrease in the compound 5a-treated mice. The infiltration of macrophages in the metastatic lesions showed a significant decrease in compound 5a-treated mice. In conclusion, the compound 5a inhibited ovary cancer cell viability and induced apoptosis through decrease in expression of vWF and metalloproteinase, suppression of FAK activation and decrease in infiltration of macrophages. The compound 5a therefore can be investigated further for the treatment of ovary cancer.
- Jia, Yan,Si, Lihui,Lin, Ruixin,Jin, Hongjuan,Jian, Wenwen,Yu, Qing,Yang, Shuli
-
-
- Multifunctional Mono-Triazole Derivatives Inhibit Aβ42 Aggregation and Cu2+-Mediated Aβ42 Aggregation and Protect against Aβ42-Induced Cytotoxicity
-
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
-
p. 1824 - 1839
(2019/09/30)
-
- Aryl Azides as Forgotten Electrophiles in the Van Leusen Reaction: A Multicomponent Transformation Affording 4-Tosyl-1-arylimidazoles
-
Considering aryl azides as electrophilic partners for the TosMIC mediated Van Leusen reaction, a novel multicomponent synthesis of 4-tosyl-1-arylimidazoles is reported. In this transformation, two molecules of TosMIC participate in the reaction mechanism
- Necardo, Cristiana,Alfano, Antonella Ilenia,Del Grosso, Erika,Pelliccia, Sveva,Galli, Ubaldina,Novellino, Ettore,Meneghetti, Fiorella,Giustiniano, Mariateresa,Tron, Gian Cesare
-
p. 16299 - 16307
(2019/12/27)
-
- Synthesis, docking and ADME prediction of novel 1,2,3-triazole-tethered coumarin derivatives as potential neuroprotective agents
-
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
-
p. 1989 - 2008
(2017/12/04)
-
- CYANO-SUBSTITUTED HETEROCYCLES WITH ACTIVITY AS INHIBITORS OF USP30
-
The present invention relates to cyano-substituted-heterocycles of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (Formula (I))
- -
-
Page/Page column 134
(2018/04/21)
-
- Design and synthesis of novel dehydroepiandrosterone analogues as potent antiproliferative agents
-
The aim of the present study was to determine the cytotoxic effects of a series of novel dehydroepiandrosterone derivatives containing triazole at the C16 position on human cancer cells. The cancer cells used in the present study were A549, Hel
- Huang, Xing,Shen, Qing-Kun,Zhang, Hong-Jian,Li, Jia-Li,Tian, Yu-Shun,Quan, Zhe-Shan
-
-
- Synthesis and biological evaluation of novel triazole-biscoumarin conjugates as potential antitubercular and anti-oxidant agents
-
Abstract: The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridization approach is described. The newly synthesized compounds 6a–k were evaluated for their in vitro antitubercular activity against active and dormant
- Danne, Ashruba B.,Choudhari, Amit S.,Sarkar, Dhiman,Sangshetti, Jaiprakash N.,Khedkar, Vijay M.,Shingate, Bapurao B.
-
p. 6283 - 6310
(2018/06/07)
-
- Synthesis of Gallic-Acid-1-Phenyl-1H-[1,2,3]Triazol-4-yl Methyl Esters as Effective Antioxidants
-
Using a click chemistry approach, a series of gallic-acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethyl esters was synthesized to develop more effective antioxidants. The results of DPPH screening indicate that few of the synthesized analogs display better antioxidant effect compared to the standards. Among all, compounds, 9 and 20 displayed highest DPPH radical scavenging effect with IC50 values as low as 6.4±0.2 and 7.9±0.4 μM respectively, compared to the standard ascorbic acid (IC50=12±0.8 μM) and gallic acid (IC50=9.0±0.6 μM). Compound 10 also displayed a potent antioxidant effect with IC50 of 10.80±0.4 μM. This study provides an important aspect with regard to the use of these gallic-acid based synthetic antioxidants in food industry as dietary supplements.
- Lone, Shabir H.,Rehman, Shakeel U,Bhat, Khursheed A.
-
p. 111 - 118
(2017/02/15)
-
- 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
-
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
-
p. 125 - 141
(2017/04/26)
-
- Synthesis method for aryl azide compound
-
The invention discloses a synthesis method for an aryl azide compound. The synthesis method includes the steps of: adding an iodo-aryl compound, sodium azide, 1,8-diazabicyclo[5.4.0]undecane-7-ene and a catalyst into a reaction container filled with a solvent, performing a stirring reaction to the reaction mixture at 60-105 DEG C with TLC tracing detection until the reaction is completed, adding ammonia water to the reaction mixture, extracting the reaction mixture for 3 times by ethyl acetate, washing the reaction mixture for 1 time by saturated salt water, drying an organic phase, performing suction filtration and spinning solvent removal, and performing column chromatographic purification to obtain a target product. The method employs easy-to-obtained raw materials and has wide selection range of copper source of the catalyst, has mild reaction condition, simple operation and high yield.
- -
-
Paragraph 0026; 0027
(2017/08/28)
-
- A comparison of novel organoiridium(III) complexes and their ligands as a potential treatment for prostate cancer
-
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.
-
p. 305 - 313
(2016/01/28)
-
- Promise of Retinoic Acid-Triazolyl Derivatives in Promoting Differentiation of Neuroblastoma Cells
-
Retinoic acid induces differentiation in various types of cells including skeletal myoblasts and neuroblasts and maintains differentiation of epithelial cells. The present study demonstrates synthesis and screening of a library of retinoic acid-triazolyl derivatives for their differentiation potential on neuroblastoma cells. Click chemistry approach using copper(I)-catalyzed azide-alkyne cycloaddition was adopted for the preparation of these derivatives. The neurite outgrowth promoting potential of retinoic acid-triazolyl derivatives was studied on neuroblastoma cells. Morphological examination revealed that compounds 8a, 8e, 8f, and 8k, among the various derivatives screened, exhibited promising neurite-outgrowth inducing activity at a concentration of 10 μM compared to undifferentiated and retinoic acid treated cells. Further on, to confirm this differentiation potential of these compounds, neuroblastoma cells were probed for expression of neuronal markers such as NF-H and NeuN. The results revealed a marked increase in the NF-H and NeuN protein expression when treated with 8a, 8e, 8f, and 8k compared to undifferentiated and retinoic acid treated cells. Thus, these compounds could act as potential leads in inducing neuronal differentiation for future studies. (Chemical Equation Presented).
- Lone, Ali Mohd,Dar, Nawab John,Hamid, Abid,Shah, Wajaht Amin,Ahmad, Muzamil,Bhat, Bilal A.
-
-
- 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
-
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
-
p. 5495 - 5508
(2016/06/01)
-
- An efficient CuI/DBU-catalyzed one-pot protocol for synthesis of 1,4-disubstituted 1,2,3-triazoles
-
A convenient CuI/DBU catalyzed one-pot method has been developed for the synthesis of 1,4-disubstituted 1,2,3-triazoles through the coupling of aryl iodides with sodium azide, followed by the intermolecular cyclization between the generated aryl azides and phenylacetaldehyde derivatives or alkynes in DMSO. The established protocol was compatible with a wide scope of substrates in good to excellent yields.
- Jiang, Yuqin,Li, Xingfeng,Zhao, Yaru,Jia, Shuhong,Li, Mingrui,Zhao, Zhiqi,Zhang, Ruili,Li, Wei,Zhang, Weiwei
-
p. 110102 - 110107
(2016/12/01)
-
- Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1-Nrf2 Protein-Protein Interaction
-
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
-
supporting information
p. 7186 - 7194
(2015/10/05)
-
- Click-tailed coumarins with potent and selective inhibitory action against the tumor-associated carbonic anhydrases IX and XII
-
Coumarins behave as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) with a mechanism of inhibition distinct from other classes of inhibitors. A series of 7-substituted coumarins incorporating aryl-triazole moieties were prepared by click chemistry procedures starting from 7-hydroxycoumarin or 4-methyl-7-aminocoumarin. The panel of new compounds was assayed for the inhibition of the cytosolic, widespread human (h) isoforms hCA I and II, and the transmembrane, tumor-associated ones hCA IX and XII. Most of the coumarins were weak inhibitors or did not inhibit significantly hCA I and II, but showed low nanomolar inhibitory action against the transmembrane isoforms (KI of 14.3-34.4 nM against hCA IX and of 4.7-37.8 nM against hCA XII). Since many hypoxic tumors overexpress hCA IX/XII, and as these targets were recently validated for obtaining antitumor/antimetastatic agents, with one inhibitor in Phase I clinical trials, the present findings constitute an interesting extension to the knowledge of non-sulfonamide, selective inhibitors of CA isoforms involved in serious pathologies.
- Nocentini, Alessio,Carta, Fabrizio,Ceruso, Mariangela,Bartolucci, Gianluca,Supuran, Claudiu T.
-
p. 6955 - 6966
(2015/11/11)
-
- Synthesis and antifungal activity of 1,2,3-triazole phenylhydrazone derivatives
-
A series of 1,2,3-triazole phenylhydrazone derivatives were designed and synthesized as antifungal agents. Their structures were determined based on 1H-NMR spectroscopy, MS, elemental analysis and X-ray single-crystal diffraction. The antifunga
- Dai, Zhi-Cheng,Chen, Yong-Fei,Zhang, Mao,Li, Sheng-Kun,Yang, Ting-Ting,Shen, Li,Wang, Jian-Xin,Qian, Shao-Song,Zhu, Hai-Liang,Ye, Yong-Hao
-
p. 477 - 486
(2015/02/02)
-
- A library of 1,2,3-triazole-substituted oleanolic acid derivatives as anticancer agents: Design, synthesis, and biological evaluation
-
A series of novel oleanolic acid coupled 1,2,3-triazole derivatives have been designed and synthesized by employing a Cu(i) catalyzed Huisgen 1,3-dipolar cycloaddition reaction. The anti-proliferative evaluation indicated that some compounds exhibited exc
- Wei, Gaofei,Luan, Weijing,Wang, Shuai,Cui, Shanshan,Li, Fengran,Liu, Yongxiang,Liu, Yang,Cheng, Maosheng
-
p. 1507 - 1514
(2015/01/30)
-
- Discovery and biological evaluation of novel 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety as c-Met kinase inhibitors
-
A series of 6,7-disubstituted-4-(2-fluorophenoxy)quinoline derivatives possessing 1,2,3-triazole-4-carboxamide moiety were designed, synthesized and evaluated for their in vitro biological activities against c-Met kinase and five typical cancer cell lines (A549, H460, HT-29, MKN-45 and U87MG). Most compounds showed moderate to excellent antiproliferative activity. In this study, a promising compound 34, with a c-Met IC50 value of 1.04 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The SAR analyses indicated that compounds with halogen group, especially fluoro group, at 4-position on the phenyl ring (moiety B) have potent antitumor activity, and methylation on the 5-atom linker played an important role in the c-Met enzymatic activity.
- Zhou, Shunguang,Liao, Huimin,Liu, Mingmei,Feng, Guobing,Fu, Baolin,Li, Ruijuan,Cheng, Maosheng,Zhao, Yanfang,Gong, Ping
-
p. 6438 - 6452
(2015/02/02)
-
- A convergent synthesis of alkyne-azide cycloaddition derivatives of 4-α,β-2-propyne podophyllotoxin depicting potent cytotoxic activity
-
A facile synthetic approach to construct the O-propargyl derivatives of 4α and 4β-(1,2,3-triazol-4-yl)-podophyllotoxin (9a-k & 10a-k) and 4′-Demethyl-4′-4β-(1,2,3-triazol-4-yl)-epipodophyllotoxin (12a-d) were synthesized by means of click chemistry. The c
- Zilla, Mahesh K.,Nayak, Debasis,Vishwakarma, Ram A.,Sharma, Parduman Raj,Goswami, Anindya,Ali, Asif
-
-
- The synthesis of some new (S)-1-aryl-N-(1-hydroxy-3-phenylpropan-2-yl)-5- methyl-1H-1,2,3-triazole-4-carboxamide
-
Some new (S)-1-aryl-N-(1-hydroxy-3-phenylpropan-2-yl)-5-methyl-1 H-1,2,3-triazole-4-carboxamides 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j have been synthesized and established by 1H and 13C NMR, IR, MS spectra, CHN analyses, and x-ray
- Shen,Chen,Wu,Dong
-
p. 781 - 786
(2013/08/23)
-
- Zinc mediated azide-alkyne ligation to 1,5- and 1,4,5-substituted 1,2,3-triazoles
-
A mild method for regioselective formation of 1,5-substituted 1,2,3-triazoles is described. The zinc-mediated reaction works at room temperature and is successful across a wide range of azido/alkynyl substrates. Additionally, the triazole 4-position can be further functionalized through the intermediate aryl-zinc to accommodate a diverse three-component coupling strategy.
- Smith, Christopher D.,Greaney, Michael F.
-
supporting information
p. 4826 - 4829
(2013/10/08)
-
- Microwave-assisted copper azide alkyne cycloaddition (CuAAC) reaction using D-glucose as a better alternative reductant
-
D-Glucose has been established as a reducing agent for the copper azide alkyne cycloaddition (CuAAC) reactions. Efficacy of this new reductant has been established against various phenyl acetylenes (14 examples) and aryl azides (16 examples). All reaction
- Kumar, Yogesh,Bahadur, Vijay,Singh, Anil K.,Parmar, Virinder S.,Singh, Brajendra K.
-
p. 1893 - 1903
(2014/01/17)
-
- Magnetically recoverable CuFe2O4 nanoparticles: Catalyzed synthesis of aryl azides and 1,4-diaryl-1,2,3-triazoles from boronic acids in water
-
Magnetically recoverable and reusable CuFe2O4 nanoparticles are shown to be highly efficient catalysts for the one-pot synthesis of biologically important 1,4-diaryl-1,2,3-triazoles starting from boronic acids, sodium azide, and acetylenes. The use of aqueous reaction medium at room temperature, the low cost and facile recovery of the catalyst by application of an external magnetic field, and consistently high catalytic efficiency for at least three consecutive cycles renders the protocol operationally attractive. Magnetic and catalytically competent CuFe 2O4 nanoparticles proved to be highly efficient in the three-component synthesis of 1,4-diaryl-1,2,3-triazoles, a class of compounds that has been recognized for its anticancer activity. Copyright
- Kumar, A. Suresh,Reddy, M. Amarnath,Knorn,Reiser,Sreedhar
-
p. 4674 - 4680
(2013/07/26)
-
- Synthesis and antimalarial activities of a diverse set of triazole-containing furamidine analogues
-
Four different series of triazole diamidines have been prepared by the Pinner method from the corresponding triazole dinitriles. Copper-catalyzed "click chemistry" was used for the synthesis of 1,4- and 4,5-substituted triazoles, aryl magnesium acetylide
- Berger, Olivier,Kaniti, Archana,van Ba, Christophe Tran,Vial, Henri,Ward, Stephen A.,Biagini, Giancarlo A.,Bray, Patrick G.,O'Neill, Paul M.
-
experimental part
p. 2094 - 2108
(2012/06/18)
-
- Synthesis of some new N-[4-acetyl-4,5-dihydro-5-(1-aryl-5-methyl-1H-1,2,3- triazol-4-yl)-5-methyl-1,3,4-thiadiazol-2-yl]acetamide derivatives
-
Several new N-[4-acetyl-4,5-dihydro-5-(1-aryl-5-methyl-1H-1,2,3-triazol-4- yl)-5-methyl-1,3,4-thiadiazol-2-yl]acetamide derivatives have been synthesized and the structures of these compounds have been established by MS, IR, CHN and 1H NMR spec
- Wang, Hui-Cheng,Li, Rong-Shan,Dong, Hong-Ru,Dong, Heng-Shan
-
scheme or table
p. 521 - 526
(2010/10/03)
-
- Nitrogen functionalities in palladium-catalyzed reactions on solid supports: A case study
-
Three different Palladium-catalyzed reactions (Heck, Suzuki, Sonogashira) were carried out on three different types of linkers on solid supports. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Knepper, Kerstin,Vanderheiden, Sylvia,Braese, Stefan
-
p. 1886 - 1898
(2007/10/03)
-
- Synthesis of some novel 3,6-bis(1,2,3-triazolyl)-s-triazolo[3,4-b]-1,3,4- thiadiazole derivatives
-
The cyclization of 1-amino-2-mercapto-5-[1-(4-ethoxyphenyl)-5-methyl-1,2,3- triazol-4-yl]-1,3,4-triazole which was synthesized from p-ethoxyaniline with various triazole acid in absolute phosphorus oxychloride yields 3,6-bis(1,2,3-triazolyl)-s-triazolo[3,
- Dong, Heng-Shan,Wang, Bin
-
p. 103 - 108
(2007/10/03)
-
- Rapid synthesis of aryl azides from aryl halides under mild conditions
-
A rapid synthesis of aryl azides from the corresponding aryl halides catalyzed by CuI/diamine is described. Sodium ascorbate was found to have a positive effect on stabilization of the catalyst system. The reactions were performed under very mild conditions generally with high yields. In the case of aryl iodides, the transformation could be carried out at room temperature. Georg Thieme Verlag Stuttgart.
- Andersen, Jacob,Madsen, Ulf,Bj?rkling, Fredrik,Liang, Xifu
-
p. 2209 - 2213
(2007/10/03)
-