915922-48-4Relevant academic research and scientific papers
COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
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Paragraph 0055; 0060; 0071, (2022/01/03)
The present invention relates to compounds of formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the present disclosure, and their use as a medicament, in particular for the treatment of ne
The development of advanced structural framework as multi-target-directed ligands for the treatment of Alzheimer's disease
Cheng, Xinfeng,Liu, Wenmin,Qiao, Zhanpin,Sang, Zhipei,Shi, Jian,Tan, Zhenghuai,Wang, Keren,Wang, Yiling,Wu, Anguo,Zhao, Yiyang,Zhu, Gaofeng
, (2020/03/03)
In this work, we have developed a novel series of multi-target-directed ligands to address low levels of acetylcholine (ACh), oxidative stress, metal ion dysregulation, and the misfolded proteins. Novel apigenin-donepezil derivatives, naringenin-donepezil derivatives, genistein-donepezil derivatives and chalcone-donepezil derivatives have been synthesized, in vitro results showed that TM-4 was a reversible and potent huAChE (IC50 = 0.36 μM) and huBChE (IC50 = 15.3 μM) inhibitor, and showed potent antioxidant activity (ORAC = 1.2 eq). TM-4 could significantly inhibit self-induced Aβ1-42 aggregation (IC50 = 3.7 μM). TM-4 was also an ideal neuroprotectant, potential metal chelation agent, and it could inhibit and disaggregate huAChE-induced and Cu2+-induced Aβ aggregation. Moreover, TM-4 could activate UPS degradation pathway in HT22 cells and induce autophagy on U87 cells to clear abnormal proteins associated with AD. More importantly, TM-4 could cross BBB in vitro assay. In addition, in vivo assay revealed that TM-4 exhibited remarkable dyskinesia recovery rate and response efficiency on AlCl3-induced zebrafish AD model, and TM-4 indicated surprising protective effect on Aβ1-40-induced vascular injury. TM-4 presented precognitive effect on scopolamine-induced memory impairment. And the regulation of multi-targets for TM-4 were further conformed through transcriptome sequencing. More interesting, the blood, urine and feces metabolism in rat and rat/human liver microsome metabolism towards TM-4 were also investigated. Overall, TM-4 is a promising multi-function candidate for the development of drugs to Alzheimer's disease.
Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease
Bai, Ping,Wang, Keren,Zhang, Pengfei,Shi, Jian,Cheng, Xinfeng,Zhang, Qi,Zheng, Cheng,Cheng, Yao,Yang, Jian,Lu, Xiaoxia,Sang, Zhipei
, (2019/10/02)
A series of novel chalcone-O-alkylamine derivatives were designed, synthesized and evaluated as multifunctional anti-Alzheimer's disease agents. Based on the experimental results, compound 23c exhibited good inhibitory potency on both acetylcholinesterase
Synthesis, antimalarial activity and cytotoxic potential of new monocarbonyl analogues of curcumin
Manohar, Sunny,Khan, Shabana I.,Kandi, Shamseer Kulangara,Raj, Kranthi,Sun, Guojing,Yang, Xiaochuan,Calderon Molina, Angie D.,Ni, Nanting,Wang, Binghe,Rawat, Diwan S.
, p. 112 - 116 (2013/02/23)
A series of novel monocarbonyl analogues of curcumin have been designed, synthesized and tested for their activity against Molt4, HeLa, PC3, DU145 and KB cancer cell lines. Six of the analogues showed potent cytotoxicity towards these cell lines with IC50 values below 1 μM, which is better than doxorubicin, a US FDA approved drug. Several analogues were also found to be active against both CQ-resistant (W2 clone) and CQ-sensitive (D6) strains of Plasmodium falciparum in an in-vitro antimalarial screening. This level of activity warrants further investigation of the compounds for development as anticancer and antimalarial agents.
