- Design, synthesis and evaluation of novel dimethylamino chalcone-O-alkylamines derivatives as potential multifunctional agents against Alzheimer's disease
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A novel series of dimethylamino chalcone-O-alkylamines derivatives was designed and synthesized as multifunctional agents for the treatment of AD. All the target compounds exhibited significant abilities to inhibit and disaggregate Aβ aggregation, and acted as potential selective AChE inhibitors, biometal chelators and selective MAO-B inhibitors. Among these compounds, compound TM-6 showed the greatest inhibitory activity against self-induced Aβ aggregation (IC50 = 0.88 μM) and well disaggregation ability toward self-induced Aβ aggregation (95.1%, 25 μM), the TEM images, molecular docking study and molecular dynamics simulations provided reasonable explanation for its high efficiency, and it was also found to be a remarkable antioxidant (ORAC-FL values of 2.1eq.), the best AChE inhibitor (IC50 = 0.13 μM) and MAO-B inhibitor (IC50 = 1.0 μM), as well as a good neuroprotectant. UV–visual spectrometry and ThT fluorescence assay revealed that compound TM-6 was not only a good biometal chelator by inhibiting Cu2+-induced Aβ aggregation (95.3%, 25 μM) but also could disassemble the well-structured Aβ fibrils (88.1%, 25 μM). Further, TM-6 could cross the blood-brain barrier (BBB) in vitro. More importantly, compound TM-6 did not show any acute toxicity in mice at doses of up to 1000 mg/kg and improved scopolamine-induced memory impairment. Taken together, these data indicated that TM-6, an excellent balanced multifunctional inhibitor, was a potential lead compound for the treatment of AD.
- Sang, Zhipei,Song, Qing,Cao, Zhongcheng,Deng, Yong,Tan, Zhenghuai,Zhang, Li
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- Silver triflate catalyzed acetylation of alcohols, thiols, phenols, and amines
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A variety of alcohols, thiols, phenols, and amines were subjected to acetylation reaction using acetic anhydride in the presence of catalytic quantity of silver triflate. The method described has a wide range of applications, proceeds under mild conditions, does not involve cumbersome workup, and the resulting products are obtained in high yields within a reasonable time. Georg Thieme Verlag Stuttgart · New York.
- Das, Rima,Chakraborty, Debashis
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experimental part
p. 1621 - 1625
(2011/06/25)
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- Oxyaniliniums as acetylcholinesterase inhibitors for the reversal of neuromuscular block
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A series of oxyanilinium-based AChE inhibitors have been synthesised and tested for the reversal of vecuronium-induced neuromuscular block. Several compounds, for example 2-hydroxy- and 2-methoxy-N,N-dimethyl-N-allylanilinium bromide (3 and 6) showed comparable reversal potencies to edrophonium and clean in vivo cardiovascular profiles.
- Grove, Simon J.A.,Kaur, Jasmit,Muir, Alan W.,Pow, Eleanor,Tarver, Gary J.,Zhang, Ming-Qiang
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p. 193 - 196
(2007/10/03)
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