93066-93-4Relevant academic research and scientific papers
Benzimidazole–galactosides bind selectively to the Galectin-8 N-Terminal domain: Structure-based design and optimisation
Hassan, Mujtaba,van Klaveren, Sjors,H?kansson, Maria,Diehl, Carl,Kova?i?, Rebeka,Baussière, Floriane,Sundin, Anders P.,Dernov?ek, Jaka,Walse, Bj?rn,Zetterberg, Fredrik,Leffler, Hakon,Anderluh, Marko,Toma?i?, Tihomir,Jakopin, ?iga,Nilsson, Ulf J.
, (2021/07/06)
We have obtained the X-ray crystal structure of the galectin-8 N-terminal domain (galectin-8N) with a previously reported quinoline–galactoside ligand at a resolution of 1.6 ?. Based on this X-ray structure, a collection of galactosides derivatised at O3 with triazole, benzimidazole, benzothiazole, and benzoxazole moieties were designed and synthesised. This led to the discovery of a 3-O-(N-methylbenzimidazolylmethyl)–galactoside with a Kd of 1.8 μM for galectin-8N, the most potent selective synthetic galectin-8N ligand to date. Molecular dynamics simulations showed that benzimidazole–galactoside derivatives bind the non-conserved amino acid Gln47, accounting for the higher selectivity for galectin-8N. Galectin-8 is a carbohydrate-binding protein that plays a key role in pathological lymphangiogenesis, modulation of the immune system, and autophagy. Thus, the benzimidazole-derivatised galactosides represent promising compounds for studies of the pathological implications of galectin-8, as well as a starting point for the development of anti-tumour and anti-inflammatory therapeutics targeting galectin-8.
Design, synthesis and biological activity of novel substituted 3-benzoic acid derivatives as MtDHFR inhibitors
Dias, Marcio Vinícius Bertacine,Ferreira, Glaucio Monteiro,Kronenberger, Thales,Parise-Filho, Roberto,Pavan, Fernando Rogério,Poso, Antti,Ribeiro, Jo?o Augusto,Tavares, Maurício Temotheo,Trossini, Gustavo Henrique Goulart,da Silva Santos, Soraya,de Souza, Alfredo Danilo Ferreira
, (2020/07/03)
The enzyme dihydrofolate reductase from M. tuberculosis (MtDHFR) has a high unexploited potential to be a target for new drugs against tuberculosis (TB), due to its importance for pathogen survival. Preliminary studies have obtained fragment-like molecule
Identification of highly potent and selective Cdc25 protein phosphatases inhibitors from miniaturization click-chemistry-based combinatorial libraries
Jing, Lanlan,Wu, Gaochan,Hao, Xia,Olotu, Fisayo A.,Kang, Dongwei,Chen, Chin Ho,Lee, Kuo-Hsiung,Soliman, Mahmoud E.S.,Liu, Xinyong,Song, Yuning,Zhan, Peng
, (2019/09/19)
Cell division cycle 25 (Cdc25) protein phosphatases play key roles in the transition between the cell cycle phases and their association with various cancers has been widely proven, which makes them ideal targets for anti-cancer treatment. Though several Cdc25 inhibitors have been developed, most of them displayed low activity and poor subtype selectivity. Therefore, it is extremely important to discover novel small molecule inhibitors with potent activities and significant selectivity for Cdc25 subtypes, not only served as drugs to treat cancer but also to probe its mechanism in transitions. In this study, miniaturized parallel click chemistry synthesis via CuAAC reaction followed by in situ biological screening were used to discover selective Cdc25 inhibitors. The bioassay results showed that compound M2N12 proved to be the most potent Cdc25 inhibitor, which also act as a highly selective Cdc25C inhibitor and was about 9-fold potent than that of NSC 663284. Moreover, M2N12 showed remarkable anti-growth activity against the KB-VIN cell line, equivalent to that of PXL and NSC 663284. An all-atom molecular dynamics (MD) simulation approach was further employed to probe the significant selectivity of M2N12 for Cdc25C relative to its structural homologs Cdc25A and Cdc25B. Overall, above results make M2N12 a promising lead compound for further investigation and structural modification.
Discovery of phenylalanine derivatives as potent HIV-1 capsid inhibitors from click chemistry-based compound library
Wu, Gaochan,Zalloum, Waleed A.,Meuser, Megan E.,Jing, Lanlan,Kang, Dongwei,Chen, Chin-Ho,Tian, Ye,Zhang, Fangfang,Cocklin, Simon,Lee, Kuo-Hsiung,Liu, Xinyong,Zhan, Peng
, p. 478 - 492 (2018/09/25)
The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of HIV-1 replication and is considered an important, clinically unexploited therapeutic target. As such, small drug-like molecules that inhibit this critical HIV-1 protein h
Axially chiral amino acid scaffolds as efficient fluorescent discriminators of methanol-ethanol
Bag, Subhendu Sekhar,Jana, Subhashis
supporting information, p. 13391 - 13398 (2017/11/28)
We report a unique fluorescence sensor based on an axially chiral unnatural triazolyl aromatic amino acid scaffold (ArTAA) for discrimination of methanol from ethanol via a switch on fluorescence response. All three sensors, the simple scaffold (ArTAA), and the mono- (PyAm-ArTAA) and bis-pyrenyl- (Py2Am-ArTAA) amides, show similar sensitivity and detection limit ranging from 0.5-2.1 v/v% of ethanol. The solid films of these sensors are also found to be effective in sensing ethanol vapour via generation of a distinct and enhanced fluorescence signal. All our experimental results suggest the role of axial chirality of the hairpin-shaped scaffold in differential solvation guided H-bonding interaction and discriminating between ethanol and methanol with a switch-on fluorescence response.
Triazolo-β-aza-ε-amino acid and its aromatic analogue as novel scaffolds for β-turn peptidomimetics
Bag, Subhendu Sekhar,Jana, Subhashis,Yashmeen, Afsana,De, Suranjan
, p. 5242 - 5245 (2015/03/30)
Triazolo-β-aza-ε-amino acid and its aromatic analogue (AlTAA/ArTAA) in the peptide backbone mark a novel class of conformationally constrained molecular scaffolds to induce β-turn conformations. This was demonstrated forAlTAA in a Leu-enkephalin analogue and in a designed pentapeptide wherein the FRET process was established. Restricted rotation induced chirality and turn conformation into the achiral aromatic amino acid scaffold,ArTAA, which in a short tripeptide backbone acted as a β-turn mimic as a β-sheet folding nucleator. This journal is
Cu (I) catalyzed alkyne-azide 1,3-dipolar cycloaddition (CuAAC): Synthesis of 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nor-testosterone-17β-yl acetates targeting progestational and antipro-liferative activities
Mohamed,El-Koussi, Nawal A.,Mahfouz, Nadia M.,Youssef, Adel F.,Abdel Jaleel, Gehad A.,Shouman, Samia A.
, p. 75 - 82 (2015/05/26)
The progestational potency and selectivity of synthetic steroidal agonists can be enhanced by even larger chemical moieties at 17α-position of the steroid backbones. Hereby a series 5a-c and 6a-c of novel 17α-[1-(substituted phenyl)-1,2,3-triazol-4-yl]-19-nortestosterone-17β-yl acetates were designed and synthesized using click chemistry approach searching progestogenic derivatives with potential anticancer activity. Compounds 5a,b and 6a,c have affected to different extents the three histopatho-logical parameters considered for evaluation of their progestational activity. The compounds 5a,b and 6a,c showed modifications in rat uterus at 35.7-34.8 nM levels with privileged endometrial thickening effect and least change of uterine weight relative to NEA at 52.9 nM level. Up to 40 mg/kg dose compounds 5b and 6c were non-toxic. Molecular docking of the ligands in PR showed in the majority of cases a conformational fitting into the active site different from that of the reference steroid NEA. Compound 6b revealed about 46.4% growth inhibition of CNS cancer SNB-75 cell line, 56% growth inhibition of renal cancer A498 cell line and 56.7% growth inhibition of prostate cancer PC-3 cell line which was mediated by cell cycle arrest. Drugability of the screened compounds showed tolerated results after being challenged to diverse physicochemical parameters.
A library of 1,2,3-triazole-substituted oleanolic acid derivatives as anticancer agents: Design, synthesis, and biological evaluation
Wei, Gaofei,Luan, Weijing,Wang, Shuai,Cui, Shanshan,Li, Fengran,Liu, Yongxiang,Liu, Yang,Cheng, Maosheng
, p. 1507 - 1514 (2015/01/30)
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
Syntheses and structure-activity relationships for some triazolyl p38α MAPK inhibitors
Seerden, Jean-Paul G.,Leusink-Ionescu, Gabriela,Leguijt, Robin,Saccavini, Catherine,Gelens, Edith,Dros, Bas,Woudenberg-Vrenken, Titia,Molema, Grietje,Kamps, Jan A.A.M.,Kellogg, Richard M.
, p. 1352 - 1357 (2014/03/21)
The design, synthesis and biological evaluation of novel triazolyl p38α MAPK inhibitors with improved water solubility for formulation in cationic liposomes (SAINT-O-Somes) targeted at diseased endothelial cells is described. Water-solubilizing groups wer
1-Phenyl-4-benzoyl-1H-1,2,3-triazoles as orally bioavailable transcriptional function suppressors of Estrogen-related receptor α
Xu, Shilin,Zhuang, Xiaoxi,Pan, Xiaofen,Zhang, Zhang,Duan, Lei,Liu, Yingxue,Zhang, Lianwen,Ren, Xiaomei,Ding, Ke
, p. 4631 - 4640 (2013/07/19)
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
