- Design, synthesis and in-vitro evaluation of fluorinated triazoles as multi-target directed ligands for Alzheimer disease
-
Alzheimer disease is multi-factorial and inflammation plays a major role in the disease progression and severity. Metals and reactive oxygen species (ROS) are the key mediators for inflammatory conditions associated with Alzheimer's. Along multi-factorial nature, major challenge for developing new drug is the ability of the molecule to cross blood brain barrier (BBB). We have designed and synthesized multi-target directed hexafluorocarbinol containing triazoles to inhibit Amyloid β aggregation and simultaneously chelate the excess metals present in the extracellular space and scavenge the ROS thus reduce the inflammatory condition. From the screened compound library, compound 1c found to be potent and safe. It has demonstrated inhibition of Amyloid β aggregation (IC50 of 4.6 μM) through selective binding with Amyloid β at the nucleation site (evidenced from the molecular docking). It also chelate metals (Cu+2, Zn+2 and Fe+3) and scavenges ROS significantly. Due to the presence of hexafluorocarbinol moiety in the molecule it may assist to permeate BBB and improve the pharmacokinetic properties. The in-vitro results of compound 1c indicate the promiscuity for the development of hexafluorocarbinol containing triazoles amide scaffold as multi-target directed therapy against Alzheimer disease.
- Dalvi, Tanay,Dewangan, Bhaskar,Agarwal, Gopal,Shinde Suchita, Dattatray,Jain, Alok,Srivastava, Akshay,Sahu, Bichismita
-
-
- Design, Synthesis, and in Vitro and in Vivo Biological Evaluation of Limonin Derivatives for Anti-Inflammation Therapy
-
In this study, limonin derivatives were used to design new anti-inflammatory compounds with high pharmacological activity and low toxicity. A total of 23 new limonin derivatives were discovered, synthesized, and screened for their anti-inflammatory activity against lipopolysaccharide (LPS)-treated RAW 264.7 cells. Of them, compound f4 was found to be the most active, with a higher efficiency compared with limonin and celecoxib. Subsequently, we studied the mechanism underlying the activity of f4 and found that it inhibited proinflammatory cytokines by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells as well as mice. In conclusion, f4 may be a promising anti-inflammatory lead compound.
- Bian, Ming,Gong, Guohua,Lei, Pang,Du, Huanhuan,Bai, Chunmei,Wei, Chengxi,Quan, Zheshan,Ma, Qianqian
-
p. 13487 - 13499
(2021/11/17)
-
- Silica immobilized copper N-heterocyclic carbene: An effective route to 1,2,3-triazoles via azide-alkyne cycloaddition and multicomponent click reaction
-
A new silica supported copper N-heterocyclic carbene (Cu-NHC@SiO2) complex is prepared and characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) analyses. This complex is an efficient and easily retrievable catalyst for 1,2,3-triazole synthesis through direct azide-alkyne cycloaddition reaction as well as one-pot reaction using arylboronic acids. This catalytic system is also suitable for synthesis of 4-aryl-NH-1,2,3-triazoles from diverse benzaldehydes. Further, the catalyst can efficiently be recycled up to fifth cycle for all the three methods of 1,2,3-triazole synthesis through direct azide-alkyne cycloaddition and multi-component reactions.
- Garg, Anirban,Borah, Nobomi,Sultana, Jasmin,Kulshrestha, Akshay,Kumar, Arvind,Sarma, Diganta
-
-
- Water Oxidation at Neutral pH using a Highly Active Copper-Based Electrocatalyst
-
The sluggish kinetics of the oxygen evolution reaction (OER) at the anode severely limit hydrogen production at the cathode in water splitting systems. Although electrocatalytic systems based on cheap and earth-abundant copper catalysts have shown promise
- Younus, Hussein A.,Zhang, Yan,Vandichel, Matthias,Ahmad, Nazir,Laasonen, Kari,Verpoort, Francis,Zhang, Ce,Zhang, Shiguo
-
p. 5088 - 5099
(2020/08/12)
-
- Co-catalyst and solvent free nitrogen rich triazole based organocatalysts for cycloaddition of CO2 into epoxide
-
A general synthesis of triazole-based catalysts remains a significant challenge. Consequently, triazole-based catalysts are rarely studied. Herein, the first report is presented for the construction of cyclic carbonates using triazole-based organocatalyst
- Elkadi, Mirella,Khattak, Zafar A. K.,Suleman, Suleman,Ullah, Habib,Verpoort, Francis,Younus, Hussein A.
-
-
- Synthesis, and evaluation of in vitro and in vivo anticancer activity of 14-substituted oridonin analogs: A novel and potent cell cycle arrest and apoptosis inducer through the p53-MDM2 pathway
-
A series of novel oridonin derivatives bearing various substituents on the 14-OH position were designed and synthesised. Their antitumour activity was evaluated in vitro against three human cancer cell lines (HCT116, BEL7402, and MCF7). Most tested derivatives showed improved anti-proliferative activity compared to the lead compound oridonin and the positive control drug 5-fluorouracil (5-Fu). Among them, compound C7 (IC50 = 0.16 μM) exhibited the most potent anti-proliferative activity against HCT116 cells; it was about 43- and 155-fold more efficacious than that of oridonin (IC50 = 6.84 μM) and 5-Fu (IC50 = 24.80 μM) in HCT116 cancer cells. Interestingly, the IC50 value of compound C7 in L02 normal cells was 23.6-fold higher than that in HCT116 cells; it exhibited better selective anti-proliferative activity and specificity than oridonin and 5-Fu. Furthermore, compound C7 possibly induced cell cycle arrest and apoptosis by regulating the p53-MDM2 signalling pathway. Notably, C7 displayed more significant suppression of tumour growth than oridonin in colon tumour xenograft models where the tumour growth inhibition rate was 85.82%. Therefore, compound C7 could be a potential lead compound for the development of a novel antitumour agent.
- Shen, Qing-Kun,Deng, Hao,Wang, Shi-Ben,Tian, Yu-Shun,Quan, Zhen-Shan
-
-
- Ag-NHC anchored on silica: An efficient ultra-low loading catalyst for regioselective 1,2,3-triazole synthesis
-
A silica-supported silver complex, Ag-NHC@SiO2, was prepared by an anchoring coordination technique, which was successfully employed for the click reaction under mild reaction conditions. The protocol offered the remarkable advantages of operat
- Garg, Anirban,Khupse, Nagesh,Bordoloi, Ankur,Sarma, Diganta
-
supporting information
p. 19331 - 19337
(2019/12/24)
-
- 4β-amidotriazole linked podophyllotoxin congeners: DNA topoisomerase-IIα inhibition and potential anticancer agents for prostate cancer
-
Topoisomerases (topo-I and topo-II) have occupied a significant role in DNA replication, transcription, and are a promising set of antitumor targets. In the present approach, a series of new 4β-amidotriazole linked podophyllotoxin derivatives (10a-i and 1
- Reddy, V. Ganga,Bonam, Srinivasa Reddy,Reddy, T. Srinivasa,Akunuri, Ravikumar,Naidu,Nayak, V. Lakshma,Bhargava, Suresh K.,Kumar, H.M. Sampath,Srihari,Kamal, Ahmed
-
p. 595 - 611
(2018/01/01)
-
- One-Pot Synthesis of 1-Monosubstituted 1,2,3-Triazoles from Propargyl Alcohol
-
A one-pot synthesis of 1-monosubstituted-1,2,3-triazoles from propargyl alcohol and various aryl azides was achieved. This simple method provides concise and efficient access to various 1-monosubstituted 1,2,3-triazole derivatives through a three-step one
- Han, Chunmei,Dong, Suping,Zhang, Wensheng,Chen, Zhen
-
p. 673 - 677
(2018/03/10)
-
- Small Molecule Inhibition of MicroRNA miR-21 Rescues Chemosensitivity of Renal-Cell Carcinoma to Topotecan
-
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
-
p. 5900 - 5909
(2018/08/04)
-
- NOVEL OXABOROLE ANALOGS AND USES THEREOF
-
This application describes compounds, compositions, and methods which are useful in treating, preventing, inhibiting, ameliorating, or eradicating the pathology and/or symptomology of a disease caused by a parasite.
- -
-
-
- Aqueous bile salt accelerated cascade synthesis of 1,2,3-triazoles from arylboronic acids
-
A facile, efficient and mild copper catalyzed strategy for cascade synthesis of various 1,4-disubstituted 1,2,3-triazoles from arylboronic acids, sodium azide and alkynes was developed by using aqueous bile salt NaDC solution as an accelerating medium. Lo
- Garg, Anirban,Ali, Abdul Aziz,Damarla, Krishnaiah,Kumar, Arvind,Sarma, Diganta
-
supporting information
p. 4031 - 4035
(2018/10/09)
-
- Catalytic Intermolecular Cross-Couplings of Azides and LUMO-Activated Unsaturated Acyl Azoliums
-
An example for the catalytic synthesis of densely functionalized 1,2,3-triazoles through a LUMO activation mode has been developed. The protocol is enabled by intermolecular cross-coupling reactions of azides with in situ-generated α,β-unsaturated acyl az
- Li, Wenjun,Ajitha, Manjaly J.,Lang, Ming,Huang, Kuo-Wei,Wang, Jian
-
p. 2139 - 2144
(2017/08/14)
-
- 4BETA-AMIDOTRIAZOLE LINKED PODOPHYLLOTOXIN DERIVATIVES AS POTENTIAL ANTICANCER AGENTS
-
The present invention relates to a compound of general formula (A). The invention provides asynthesis of new 4β-amidotriazole linked podophyllotoxin derivatives of general formulae 8a-z to 9a-z useful as potential anticancer agents against human cancer ce
- -
-
-
- Discovery of a novel 6,7-disubstituted-4-(2-fluorophenoxy)quinolines bearing 1,2,3-triazole-4-carboxamide moiety as potent 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 cytotoxic activities against four typical cancer cell lines (A549, H460, HT-29, and MKN-45). Most compounds showed moderate-to-excellent antiproliferative activity. Compounds 32, 36, 37, 45, 51, and 52 were further examined for their inhibitory activity against c-Met kinase. The promising compound 37, with a c-Met IC50 value of 2.27 nM, was identified as a multitargeted receptor tyrosine kinase inhibitor. The analysis of their structure-activity relationships indicated that compounds with EWGs, especially chloro group, at 2-position on the phenyl ring (moiety B) have potent antitumor activity.
- Liu, Mingmei,Hou, Yunlei,Yin, Weile,Zhou, Shunguang,Qian, Ping,Guo, Zhuang,Xu, Liying,Zhao, Yangfang
-
-
- Triazole containing novobiocin and biphenyl amides as Hsp90 C-terminal inhibitors
-
Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is a major detriment associated with
- Zhao, Jinbo,Zhao, Huiping,Hall, Jessica A.,Brown, Douglas,Brandes, Eileen,Bazzill, Joseph,Grogan, Patrick T.,Subramanian, Chitra,Vielhauer, George,Cohen, Mark S.,Blagg, Brian S. J.
-
supporting information
p. 1317 - 1323
(2014/10/15)
-
- One-pot synthesis of 1,2,3-triazoles from boronic acids in water using Cu(ii)-β-cyclodextrin complex as a nanocatalyst
-
We report here the one-pot synthesis of 1,2,3-triazoles of arylboronic acids in water. An efficient method has been developed for the synthesis of 1,2,3-triazoles via a one-pot reaction of an arylboronic acid with sodium azide in the presence of Cu2-β-CD (CD = Cyclodextrin) as a nanocatalyst in water followed by a click cyclization reaction with an alkyne at room temperature in air without any additives. This method is simple, rapid, and high yielding.
- Kaboudin, Babak,Abedi, Yaghoub,Yokomatsu, Tsutomu
-
p. 4543 - 4548
(2012/07/17)
-
- Tandem catalysis: From alkynoic acids and aryl iodides to 1,2,3-triazoles in one pot
-
A tandem catalysis protocol based on decarboxylative coupling of alkynoic acids and 1,3-dipolar cycloaddition of azides enables a highly efficient synthesis of a variety of functionalized 1,2,3-triazoles. The three-step, one-pot method avoids usage of gas
- Kolarovic, Andrej,Schnuerch, Michael,Mihovilovic, Marko D.
-
scheme or table
p. 2613 - 2618
(2011/06/17)
-
- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-COA DESATURASE
-
The present invention relates to piperazine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
-
Page/Page column 16
(2010/07/04)
-
- Boronic acid catalysis for mild and selective [3+2] dipolar cycloadditions to unsaturated carboxylic acids
-
Herein, the concept of boronic acid catalysis (BAC) for the activation of unsaturated carboxylic acids is applied in several classic dipolar [3 + 2] cycloadditions involving azides, nitrile oxides, and nitrones as partners. These cycloadditions can be used to produce pharmaceutically interesting, small heterocyclic products, such as triazoles, isoxazoles, and isoxazolidines. These cycloadducts are formed directly and include a free carboxylic acid functionality that can be employed for fur-ther transformations, thereby avoiding prior masking or functionalization. In all cases, BAC provides faster reactions, under milder conditions, with much improved product yields and regioselectivities. In some instances, such as triazole formation from the reaction of azides with 2-alkynoic acids, catalysis with ort/io- nitrophenylboronic acid circumvents the undesirable product decarboxylation observed when using thermal activation. By using NMR spectroscopic studies, the boronic acid catalyst was shown to provide activation by a LUMO-lowering effect in the unsaturated carboxylic acid, likely via a monoacylated hemiboronic ester intermediate.
- Zheng, Hongchao,McDonald, Robert,Hall, Dennis G.
-
experimental part
p. 5454 - 5460
(2010/09/15)
-
- NOVEL PIPERAZINE DERIVATIVES AS INHIBITORS OF STEAROYL-CoA DESATURASE
-
The present invention relates to piperidine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.
- -
-
Page/Page column 74-75
(2009/10/01)
-
- Synthesis and antibiotic activity of a small molecules library of 1,2,3-triazole derivatives
-
A small library of simple 1,4-disubstituted 1,2,3-triazoles was prepared using a known one-pot procedure starting from organic halides and terminal alkynes. The compounds were then tested for their antibacterial activity against normal and resistant speci
- Aufort, Marie,Herscovici, Jean,Bouhours, Pascale,Moreau, Nicole,Girard, Christian
-
p. 1195 - 1198
(2008/12/21)
-
- Synthesis of aminoquinolones from triazoles via carboxamido-ketenimine and amidinoketene intermediates
-
1-Aryl-1H-1,2,3-triazole-4-carboxamides 7d-f have been synthesized and converted to 2-dimethylamino-4-quinolones 12d-f by flash vacuum thermolysis (FVT). The reaction takes place via carboxamidoketenimine 9 and amidinoketene intermediates 10. The former are observed by FTIR spectroscopy at 77 K or in Ar matrices at 12 K.
- Rao, V.V. Ramana,Wentrup, Curt
-
p. 2583 - 2586
(2007/10/03)
-
- UNSATURATED CARBONYL-CONTAINING COMPOUNDS. XXVIII. CYCLOADDITION OF ORGANIC AZIDES TO α-ACETYLENIC KETONES AND ACIDS
-
The reaction of α-acetylenic ketones and acids with organic azides leads to the formation of 1-alkyl(aryl)-4-acyl(carboxy)-1,2,3-triazoles or to a mixture of the 1,4- and 1,5-disubstituted isomers.The effect of the structure of the initial compound and of the solvent on the direction of cycloaddition was investigated.
- Vereshchagin, L. I.,Tikhonova, L. G.,Maksikova, A. V.,Serebryakova, E. S.,Proidakov, A. G.,Filippova, T. M.
-
p. 641 - 648
(2007/10/02)
-