- An environment-friendly synthesis of piperonal chalcones and their cytotoxic and antioxidant evaluation
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Background: Grindstone technique has been widely used as an efficient, consistent, more environmentally benign, solvent-free protocol for the preparation of many compounds with higher atom economy. Methods: A series of fourteen piperonal chalcone compound
- Baby, Bency,Dev, Sanal,Joy, Monu,Magdy, Hendawy Omnia,Mathew, Bijo,Mathew, Githa Elizabeth,Parambi, Della Grace Thomas,Sudev, Shine
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p. 138 - 144
(2020/02/29)
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- Design, synthesis, and evaluation of 1, 4-benzodioxan-substituted chalcones as selective and reversible inhibitors of human monoamine oxidase B
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The inhibition of monoamine oxidase B (MAO-B) could be an effective approach for the treatment of various neurological disorders. In this study, a series of 1, 4-benzodioxan-substituted chalcone derivatives were designed, synthesised and evaluated for the
- Kong, Zhuo,Sun, Demeng,Jiang, Yanmei,Hu, Yun
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p. 1513 - 1523
(2020/07/30)
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- Discovery of new fluorescent thiazole–pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells
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A series of fluorescent thiazole–pyrazoline derivatives was synthesized and their structures were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growt
- Chen, Yuan,Gao, DongFang,Kong, Feng,Lin, YuXing,Lin, ZhaoMin,Miao, JunYing,Wang, Peng,Wang, ZhaoYang,Zhang, Lu,Zhang, Ming,Zhao, BaoXiang,Zhou, XueWen
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- Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti-inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia
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We previously reported Chalcone-4 (1) that binds the chemokine CXCL12, not its cognate receptors CXCR4 or CXCR7, and neutralizes its biological activity. However, this neutraligand suffers from limitations such as poor chemical stability, solubility, and oral activity. Herein, we report on the discovery of pyrimidinone 57 (LIT-927), a novel neutraligand of CXCL12 which displays a higher solubility than 1 and is no longer a Michael acceptor. While both 1 and 57 reduce eosinophil recruitment in a murine model of allergic airway hypereosinophilia, 57 is the only one to display inhibitory activity following oral administration. Thereby, we here describe 57 as the first orally active CXCL12 neutraligand with anti-inflammatory properties. Combined with a high binding selectivity for CXCL12 over other chemokines, 57 represents a powerful pharmacological tool to investigate CXCL12 physiology in vivo and to explore the activity of chemokine neutralization in inflammatory and related diseases.
- Regenass, Pierre,Abboud, Dayana,Daubeuf, Fran?ois,Lehalle, Christine,Gizzi, Patrick,Riché, Stéphanie,Hachet-Haas, Muriel,Rohmer, Fran?ois,Gasparik, Vincent,Boeglin, Damien,Haiech, Jacques,Knehans, Tim,Rognan, Didier,Heissler, Denis,Marsol, Claire,Villa, Pascal,Galzi, Jean-Luc,Hibert, Marcel,Frossard, Nelly,Bonnet, Dominique
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supporting information
p. 7671 - 7686
(2018/09/06)
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- Design, synthesis and biological evaluation of novel pyrazoline-containing derivatives as potential tubulin assembling inhibitors
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Abstract A series of novel pyrazoline-containing derivatives (15-47) has been designed, synthesized and evaluated for their biological activities. Among them, compound 18 displayed the most potent antiproliferative activity against A549, MCF-7 and HepG-2 cells line (IC50 Combining double low line 0.07 μM, 0.05 μM, 0.03 μM, respectively) and the tubulin polymerization inhibitory activity (IC50 Combining double low line 1.88 μM), being comparable to CA-4. Furthermore, we also tested that compound 18 was a potent inducer of apoptosis in HepG-2 cells and it had cellular effects typical for microtubule interacting agents, causing accumulation of cells in the G2/M phase of the cell cycle. These studies, along with molecular docking, provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
- Qin, Ya-Juan,Li, Yu-jing,Jiang, Ai-Qin,Yang, Meng-Ru,Zhu, Qi-Zhang,Dong, Hong,Zhu, Hai-Liang
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p. 447 - 457
(2015/04/14)
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- 4,5-Dihydropyrazole derivatives containing oxygen-bearing heterocycles as potential telomerase inhibitors with anticancer activity
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Telomere and telomerase were closely related to the occurrence and development of some cancers. After the key active site of telomerase was identified, to enhance the ability of dihydropyrazole derivatives to inhibit telomerase, we designed a series of novel 4,5-dihydropyrazole derivatives containing heterocyclic oxygen moiety based on previous studies. The telomerase inhibition assay showed that compound 10a displayed the most potent inhibitory activity with an IC50 value of 0.6 μM for telomerase. The antiproliferative assay showed that 10a exhibited high activity against human gastric cancer cell SGC-7901 with an IC50 value of 10.95 ± 0.60 μM. Flow cytometric analysis and western blot results showed that 10a induced both apoptosis and autophagy. A docking simulation showed that 10a could bind well to the active site of telomerase and act as a telomerase inhibitor. The 3D-QSAR model was also built to provide a more pharmacological understanding that could be used to design new agents with more potent telomerase inhibitory activity.
- Luo, Yin,Zhou, Yang,Fu, Jie,Zhu, Hai-Liang
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p. 23904 - 23913
(2014/07/07)
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- Synthesis and cdc25B inhibitory activity evaluation of chalcones
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A library of sixty-five chalcones was prepared for screening against the protein phosphatase, cdc25B. From this library, thirteen compounds were found having good inhibitory activity. Two compounds have excellent activity and can be used for the design of
- Zhao, Fei,Zhao, Qing-Jie,Zhao, Jing-Xia,Zhang, Da-Zhi,Wu, Qiu-Ye,Jin, Yong-Sheng
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p. 206 - 214
(2013/07/26)
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- Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives containing benzodioxole as potential anticancer agents
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A series of novel thiazolyl-pyrazoline derivatives containing benzodioxole (C1-C20) have been designed and synthesized. Among of the synthesized compounds, 2-(5-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-1-yl)- 4-(4-bromophenyl)thiazole (C6) displayed the most potent inhibitory activity for HER-2 (IC50 = 0.18 μM for HER-2). Antiproliferative assay results indicated that compound C6 owned high antiproliferative activity against MCF-7 and B16-F10 in vitro, with IC50 value of 0.09 and 0.12 μM, respectively, being comparable with the positive control Erlotinib. Docking simulation was further performed to determine the probable binding model. Based on the preliminary results, compound C6 with potent inhibitory activity in tumor growth would be a potential anticancer agent.
- Wang, Hai-Hong,Qiu, Ke-Ming,Cui, Hong-En,Yang, Yu-Shun,Yin-Luo,Xing, Man,Qiu, Xiao-Yang,Bai, Li-Fei,Zhu, Hai-Liang
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p. 448 - 455
(2013/02/25)
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- Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors
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A series of novel aryl-2H-pyrazole derivatives bearing 1,4-benzodioxan or 1,3-benzodioxole moiety were designed as potential telomerase inhibitors to enhance the ability of aryl-2H-pyrazole derivatives to inhibit telomerase, a target of anticancer. The telomerase inhibition tests showed that compound 16A displayed the most potent inhibitory activity with IC50 value of 0.9 μM for telomerase. The antiproliferative tests showed that compound 16A exhibited high activity against human gastric cancer cell SGC-7901 and human melanoma cell B16-F10 with IC50 values of 18.07 and 5.34 μM, respectively. Docking simulation showed that compound 16A could bind well with the telomerase active site and act as telomerase inhibitor. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent telomerase inhibitory activity.
- Luo, Yin,Zhang, Shuai,Qiu, Ke-Ming,Liu, Zhi-Jun,Yang, Yu-Shun,Fu, Jie,Zhong, Wei-Qing,Zhu, Hai-Liang
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p. 1091 - 1095
(2013/03/13)
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- Synthesis of 1-substituted 3-aryl-5-aryl(hetaryl)-2-pyrazolines and study of their antitumor activity
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Three series of novel 1,3,5-trisubstituted 2-pyrazoline derivatives containing thiophene and benzodioxol moieties as potential antitumor agents were synthesized. The in vitro antitumor activity of the obtained compounds was determined at the National Canc
- Insuasty, Braulio,Chamizo, Leidy,Munoz, Jhon,Tigreros, Alexis,Quiroga, Jairo,Abonia, Rodrigo,Nogueras, Manuel,Cobo, Justo
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scheme or table
p. 275 - 286
(2012/06/30)
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- Study on the substituents' effects of a series of synthetic chalcones against the yeast Candida albicans
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A large series of chalcones were synthesized and studied for activity against Candida albicans. The SAR analysis showed that the antifungal activity was highly dependent on the substitution pattern of the aryl rings and correlated to a large extent with the ability of compounds to interact with sulfhydryl groups. The most active were the hydroxylated chalcones as their activity related to the location of the phenolic group in the aryl ring B as follows: o-OH > p-OH ~ 3,4-di-OH > m-OH. These and other correlations obtained strongly contribute to the knowledge for design of anticandidal chalcones.
- Batovska,Parushev,Slavova,Bankova,Tsvetkova,Ninova,Najdenski
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- Structure-activity relationships in a series of orally active γ- hydroxy butenolide endothelin antagonists
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The design of potent and selective non-peptide antagonists of endothelin-1 (ET-1) and its related isopeptides are important tools defining the role of ET in human diseases. In this report we will describe the detailed structure-activity relationship (SAR) studies that led to the discovery of a potent series of butenolide ET(A) selective antagonists. Starting from a micromolar screening hit, PD012527, use of Topliss decision tree analysis led to the discovery of the nanomolar ET(A) selective antagonist PD155080. Further structural modifications around the butenolide ring led directly to the subnanomolar ET(A) selective antagonist PD156707, IC50's = 0.3 (ET(A)) and 780 nM (ET(B)). This series of compounds exhibited functional activity exemplified by PD156707. This derivative inhibited the ET(A) receptor mediated release of arachidonic acid from rabbit renal artery vascular smooth muscle cells with an IC50 = 1.1 nM and also inhibited the ET-1 induced contraction of rabbit femoral artery rings (ET(A) mediated) with a pA2 = 7.6. PD156707 also displayed in vivo functional activity inhibiting the hemodynamic responses due to exogenous administration of ET-1 in rats in a dose dependent fashion. Evidence for the pH dependence of the open and closed tautomerization forms of PD156707 was demonstrated by an NMR study. X- ray crystallographic analysis of the closed butenolide form of PD156707 shows the benzylic group located on the same side of the butenolide ring as the γ- hydroxyl and the remaining two phenyl groups on the butenolide ring essentially orthogonal to the butenolide ring. Pharmacokinetic parameters for PD156707 in dogs are also presented.
- Patt, William C.,Edmunds, Jeremy J.,Repine, Joseph T.,Berryman, Kent A.,Reisdorph, Billy R.,Lee, Chet,Plummer, Mark S.,Shahripour, Aurash,Haleen, Stephen J.,Keiser, Joan A.,Flynn, Mike A.,Welch, Kathleen M.,Reynolds, Elwood E.,Rubin, Ron,Tobias, Brian,Hallak, Hussein,Doherty, Annette M.
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p. 1063 - 1074
(2007/10/03)
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