1262136-39-9Relevant academic research and scientific papers
Design, Synthesis, and Biological Evaluation of Coupled Bioactive Scaffolds as Potential Anticancer Agents for Dual Targeting of Dihydrofolate Reductase and Thioredoxin Reductase
Ng, Hui-Li,Ma, Xiang,Chew, Eng-Hui,Chui, Wai-Keung
, p. 1734 - 1745 (2017/03/17)
The dihydrofolate reductase (DHFR) and thioredoxin reductase (TrxR) enzymes are involved in the process of tumor cell growth and survival. The 4,6-diamino-1,2-dihydro-1,3,5-triazine scaffold is well-established as a useful scaffold for DHFR inhibition, while chalcones have been reported to be inhibitors of TrxR. In this study, 15 novel compounds designed by the structural combination of the 4,6-diamino-1,2-dihydro-1,3,5-triazine and chalcone scaffolds via a diether linker were successfully synthesized and characterized. All of the compounds demonstrated dual inhibition against DHFR and TrxR when they were assessed by in vitro enzyme assays. The compounds also exhibited antiproliferative activity against the MCF-7 and HCT116 cells. The more potent analogs 14 and 15 were found to inhibit cellular DHFR and TrxR activities in HCT116 cells. Therefore, this study provided compelling evidence that 14 and 15 could exert their anticancer property via multitarget inhibition at the cellular level.
Design, synthesis and pharmacological evaluation of chalcone derivatives as acetylcholinesterase inhibitors
Liu, Hao-Ran,Liu, Xian-Jun,Fan, Hao-Qun,Tang, Jing-Jing,Gao, Xiao-Hui,Liu, Wu-Kun
, p. 6124 - 6133 (2015/01/08)
A novel series of chalcone derivatives (4a-8d) were designed, synthesized, and evaluated for the inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The log P values of the compounds were shown to range from 1.49 to 2.19, which suggested that they were possible to pass blood brain barriers in vivo. The most promising compound 4a (IC50: 4.68 μmol/L) was 2-fold more potent than Rivastigmine against AChE (IC50: 10.54 μmol/L) and showed a high selectivity for AChE over BuChE (ratio: 4.35). Enzyme kinetic study suggested that the inhibition mechanism of compound 4a was a mixed-type inhibition. Meanwhile, the result of molecular docking showed its potent inhibition of AChE and high selectivity for AChE over BuChE.
Syntheses and reactions of 4'-[(ω-bromoalkyl)oxy]-and 4',4'''-(polymethylenedoxy)-bis substituted chalcones
Sodani,Choudhary, Prakash C.,Sharma, Hari Om,Verma
experimental part, p. 763 - 769 (2011/11/14)
Base catalyzed condensation of 4-hydroxyacetophenone (1) with several aldehydes resulted 4'-hydroxychalcones (2a-c). Reaction of α,ω-dibromoalkanes (3, n=2, 4 & 6) with (2a-c) in equimolar ratio resulted a mixture of 4'-[(ω-bromoalkyl)oxy]- substituted chalcones (4a-i) and 4',4'''-(polymethylenedioxy)-bis substituted chalcones (5a-i) separated by ethanol as soluble (4a-i) and insoluble (5a-i) products. Compounds (5a-i) were also synthesized by another route. Compound 1 on treatment with 3 in molar ratio 2:1 resulted 4',4'''-(polymethylenedioxy)-diacetophenone (4#a-c) which on base catalyzed condensation gave compounds (5a-i). Reaction of 4d with substituted phenols and thiophenols gave corresponding phenoxy and thiophenoxy substituted chalcones (6a-f) where as compounds 5a, 5b, 5d, 5h and 5e on treatment with hydrazine hydrate furnished corresponding bis-2-pyrazolines (7a-e). The structures of all synthesized compounds were confirmed on the basis of analytical and spectral data.
