55727-53-2Relevant articles and documents
Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer's disease
Manzoor, Shoaib,Gabr, Moustafa T.,Rasool, Bisma,Pal, Kavita,Hoda, Nasimul
, (2021/09/28)
Development of multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for Alzheimer's disease (AD). Herein, we reported a new series of deoxyvasicinone analogues as dual inhibitor of acetylcholinesterase (AChE) and tau aggregation that function as multitargeted ligands for AD. All the multitargeted ligands 11(a-j) and 15(a-g) were designed, synthesized, and validated by 1HNMR, 13CNMR and mass spectrometry. All the synthesized compounds 11(a-j) and 15(a-g) were screened for their ability to inhibit AChE, BACE1, amyloid fibrillation, α-syn aggregation, and tau aggregation. All the screened compounds possessed weak inhibition of BACE-1, Aβ42 and α-syn aggregation. However, several compounds were identified as potential hits in the AChE inhibitory screening assay and cellular tau aggregation screening. Among all compounds, 11f remarkably inhibited AChE activity and cellular tau oligomerization at single-dose screening (10 μM). Moreover, 11f displayed a half-maximal inhibitory concentration (IC50) value of 0.91 ± 0.05 μM and half-maximal effective concentration (EC50) value of 3.83 ± 0.51 μM for the inhibition of AChE and cellular tau oligomerization, respectively. In addition, the neuroprotective effect of 11f was determined in tau-expressing SH-SY5Y cells incubated with Aβ oligomers. These findings highlighted the potential of 11f to function as a multifunctional ligand for the development of promising anti-AD drugs.
Novel Deoxyvasicinone-Donepezil Hybrids as Potential Multitarget Drug Candidates for Alzheimer's Disease
Du, Hongtao,Liu, Xinlian,Xie, Jusen,Ma, Fang
, p. 2397 - 2407 (2019/03/07)
In this study, we designed and synthesized a series of deoxyvasicinone-donepezil hybrids and determined whether they could be used as novel multitarget inhibitors for Alzheimer's disease. In vitro studies showed that most of the hybrids demonstrated moderate to potent inhibition of hAChE, BACE1, and Aβ1-42 aggregation. In particular, the hybrids 10a, 10d, 11a, and 11j exhibited excellent inhibitory activities against hAChE (IC50 = 56.14, 5.91, 3.29, and 8.65 nM, respectively), BACE1 (IC50 = 0.834, 0.167, 0.129, and 0.085 μM, respectively), and Aβ1-42 aggregation (IC50 = 13.26, 19.43, 9.26, and 5.41 μM, respectively). In addition, 10a and 11a exhibited very low cytotoxicity and showed remarkable neuroprotective activity against Aβ1-42-induced damage in SH-SY5Y cells.
Directions of reactions of 6-amino-, -acetylamino-, and- benzoylaminodeoxyvasicinones with aldehydes
Elmuradov,Abdurazakov,Shakhidoyatov
experimental part, p. 262 - 267 (2010/09/18)
6-Acetylamino- and -benzoylamino-9-arylidenedeoxyvasicinones were synthesized by reaction of 6-amino-(3), -acetylamino- (4), and -benzoylamino- (5) -deoxyvasicinones (DOV) with aromatic aldehydes and furfurol in glacial acetic acid. It was shown that the amino group of 6-aminodeoxyvasicinone underwent acylation upon reaction with aldehydes to form 6-acetylamino-DOV, which reacted with aldehydes to form 9-arylidene derivatives. Carrying out this condensation in toluene, o-xylene, and ethanol produced a mixture of condensation products at the 6-amino- and α-CH2-groups. It was found that condensati on of 3 with 4-nitrobenzaldehyde in pyridine formed exclusively the Schiff bases. Methods for preparing 6-nitrodeoxyvasicinone and for its reduction were improved.
