- Looking toward the Rim of the Active Site Cavity of Druggable Human Carbonic Anhydrase Isoforms
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We report the synthesis and biochemical evaluation of a series of substituted 4-(4-aroylpiperazine-1-carbonyl)benzenesulfonamides (5a-s) developed as inhibitors of druggable carbonic anhydrase (CA) isoforms, as tools for the identification of new therapeu
- Mancuso, Francesca,Di Fiore, Anna,De Luca, Laura,Angeli, Andrea,Monti, Simona M.,De Simone, Giuseppina,Supuran, Claudiu T.,Gitto, Rosaria
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supporting information
p. 1000 - 1005
(2020/03/23)
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- Synthesis, characterization, and anti-inflammatory activities of methyl salicylate derivatives bearing piperazine moiety
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In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents.
- Li, Jingfen,Yin, Yong,Wang, Lisheng,Liang, Pengyun,Li, Menghua,Liu, Xu,Wu, Lichuan,Yang, Hua
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- Expanding the structural diversity of Bcr-Abl inhibitors: Hybrid molecules based on GNF-2 and Imatinib
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In order to expand the structural diversity of Bcr-Abl inhibitors, twenty hybrids (series E and P) have been synthesized and characterized based on Imatinib and GNF-2. Their biological activities were evaluated in vitro against human leukemia cells. Most compounds exhibited potent antiproliferative activity against K562 cells, especially for compounds E4, E5 and E7. Furthermore, these new hybrids were also screened for Abl kinase inhibitory activity, and some of them inhibited Abl kinase with low micromolar IC50 values. In particular, compound P3 displayed the most potent activity with IC50 value of 0.017 μM comparable with that of Imatinib. Molecular docking studies indicated that these novel hybrids fitted well with the active site of Bcr-Abl. These results suggested the great potential of these compounds as novel Bcr-Abl inhibitors.
- Pan, Xiaoyan,Dong, Jinyun,Shao, Ruili,Su, Ping,Shi, Yaling,Wang, Jinfeng,He, Langchong
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supporting information
p. 4164 - 4168
(2015/11/03)
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- Discovery of novel Bcr-Abl inhibitors targeting myristoyl pocket and ATP site
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Bcr-Abl plays an essential role in the pathogenesis and development of chronic myeloid leukaemia (CML). Inhibition of Bcr-Abl has great potential for therapeutic intervention in CML. In order to obtain novel and potent Bcr-Abl inhibitors, twenty seven 4,6-disubstituted pyrimidines were synthesized and evaluated herein. The biological results indicated that four compounds of them (C4, C5, C16, and C23) were potent Bcr-Abl inhibitors which were comparable to positive control. Moreover, C4 and C5 displayed promising antiproliferative activity against K562 cells. The results suggested that these 4,6-disubstituted pyrimidines could serve as promising leads for further optimization of Bcr-Abl inhibitors.
- Dong, Jinyun,Lu, Wen,Pan, Xiaoyan,Su, Ping,Shi, Yaling,Wang, Jinfeng,Zhang, Jie
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p. 6876 - 6884
(2015/01/09)
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- Synthesis and evaluation of meta substituted 1-(aryloxypropyl)-4- (chloroaryl) piperazines as potential atypical antipsychotics
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A series of 1-(aryloxypropyl)-4-(chloroaryl) piperazines have been synthesized based upon their physicochemical similarity with respect to standard atypical antipsychotic drugs and their potential to cross the blood-brain barrier (log BB) as calculated by
- Bali, Alka,Reddy, A. C. Dinesh Kumar
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p. 382 - 391
(2013/03/13)
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- Synthesis, evaluation and computational studies on a series of acetophenone based 1-(aryloxypropyl)-4-(chloroaryl) piperazines as potential atypical antipsychotics
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A series of 1-(aryloxypropyl)-4-(chloroaryl) piperazines have been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypy assays in mice. The compounds 11 and 12 have emerged
- Bali, Alka,Sharma, Komal,Bhalla, Abhishek,Bala, Suman,Reddy, Dinesh,Singh, Anant,Kumar, Anil
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experimental part
p. 2656 - 2662
(2010/07/09)
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