- Synthesis and in vitro anti-bladder cancer activity evaluation of quinazolinyl-arylurea derivatives
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Based on the structural modification of molecular-targeted agent sorafenib, a series of quinazolinyl-arylurea derivatives were synthesized and evaluated for their anti-proliferative activities against six human cancer cell lines. Compared with other cell lines tested, T24 was more sensitive to most compounds. Compound 7j exhibited the best profile with lower IC50 value and favorable selectivity. In this study, we focused on 7j-induced death forms of T24 cells and tried to elucidate the reason for its potent proliferative inhibitory activity. Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j: (1) Lower concentrations within the initial 8 h of 7j treatment led to apoptosis-dependent death. (2) Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc?/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. (3) The above death forms were closely associated with intracellular ROS generation and decreased mitochondrial membrane potential induced by 7j. In molecular docking and structure-activity relationship analyses, 7j could bind well to the active site of the corresponding receptor glutathione peroxidase 4 (GPx4). Compound 7j could be a promising lead for molecular-targeted anti-bladder cancer agents’ discovery.
- Chen, Jia-Nian,Li, Ting,Cheng, Li,Qin, Tai-Sheng,Sun, Ye-Xiang,Chen, Chu-Ting,He, Yue-Zhen,Liu, Guang,Yao, Di,Wei, Ying,Li, Qiu-Yin,Zhang, Guang-Ji
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- Palladium-catalyzed synthesis of N-aryl carbamates
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An efficient synthesis of aryl carbamates was achieved by introducing alcohols into the reaction of palladium-catalyzed cross-coupling of ArX (X = Cl, OTf) with sodium cyanate. The use of aryl triflates as electrophilic components in this transformation a
- Vinogradova, Ekaterina V.,Park, Nathaniel H.,Fors, Brett P.,Buchwald, Stephen L.
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supporting information
p. 1394 - 1397
(2013/04/24)
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- Synthesis and in vitro antitumor activity of novel diaryl urea derivatives
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A series of novel diaryl ureas containing 4-[(2-amino-6-trifluromethyl) pyrimidine-4-yl]piperazine-1-yl group were synthesized and evaluated for their cytotoxic activities in a panel of human cancer cell lines. Compared with the reference drug Sorafenib, some compounds showed more potent and a broader spectrum of anti-cancer activities. Among them, compound 2p demonstrated significant inhibitory activities against MDA-MB-231, HT-29 and MCF-7 cell lines with IC50 values of 0.016, 0.63, 0.001 μmol/L, respectively.
- Zhao, Yan-Fang,Liu, Zi-Jian,Zhai, Xin,Ge, Dan-Dan,Huang, Qiang,Gong, Ping
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p. 386 - 388
(2013/07/19)
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- Synthesis of aryl urea derivatives from aryl amines and aryl isocyanates
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The present study describes the synthesis of novel diaryl urea derivatives derived from aryl amine and aryl isocyanates. The synthesized compounds are analogs of sorafenib [4-[4-[[[4-chloro-3-(trifluoromethyl)phenyl]amino]carbonyl] amino]phenoxy]-N-methylpyridine-2- carboxamide] having potential antiproliferative activity.
- Usharani,Bhujanga Rao,Reddy,Dubey
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experimental part
p. 1802 - 1806
(2011/12/22)
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- Methyl analogues of the experimental Alzheimer drug phenserine: Synthesis and structure/activity relationships for acetyl- and butyrylcholinesterase inhibitory action
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With the goal of developing potential Alzheimer's pharmacotherapeutics, we have synthesized a series of novel analogues of the potent anticholinesterases phenserine (2) and physostigmine (1). These derivatives contain methyl (3, 4, 6), dimethyl (5, 7, 8, 10, 11) and trimethyl (14) substituents in each position of the phenyl group of the phenylcarbamoyl moieties, and with N-methyl and 6-methyl substituents (12, 13, 31, 33). We also quantified the inhibitory action of these compounds against human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). An analysis of the structure/anticholinesterase activity relationship of the described compounds, together with molecular modeling, confirmed the catalytic triad mechanism of the binding of this class of carabamate analogues within AChE and BChE and defined structural requirements for their differential inhibition.
- Yu,Holloway,Flippen-Anderson,Hoffman,Brossi,Greig
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p. 4062 - 4071
(2007/10/03)
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