Category: bromides-buliding-blocksIn 2021 ,《Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer′s disease》 was published in Bioorganic Chemistry. The article was written by Zhang, Panpan; Wang, Ze; Mou, Chenye; Zou, Jiamei; Xie, Yanfei; Liu, Zhiwen; Benjamin Naman, C.; Mao, Yuechun; Wei, Jiaxin; Huang, Xinghan; Dong, Jiahui; Yang, Mengxiang; Wang, Ning; Jin, Haixiao; Liu, Fufeng; Lin, Dongdong; Liu, Hao; Zhou, Fei; He, Shan; Zhang, Bin; Cui, Wei. The article contains the following contents:
Alzheimer′s disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an β-amyloid (Aβ) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Aβ1-42 aggregation in vitro, and 13a exhibited nanomolar level inhibition. Mol. docking anal. suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Aβ1-42 pentamers. Moreover, 13a effectively attenuated Aβ1-42 oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.Methyl 3-bromopropanoate(cas: 3395-91-3Category: bromides-buliding-blocks) was used in this study.
Methyl 3-bromopropanoate(cas: 3395-91-3) belongs to bromides. One prominent application of synthetic organobromine compounds is the use of polybrominated diphenyl ethers as fire-retardants, and in fact fire-retardant manufacture is currently the major industrial use of the element bromine.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary