Discovery of novel benzofuran-based compounds with neuroprotective and immunomodulatory properties for Alzheimer's disease treatment

GC/MSn analysis of the crude reaction mixtures from Friedel–Crafts acylation: Unambiguous identification and differentiation of 3‐aroylbenzofurans from their 4‐ and 6‐regioisomers

“…9 Hence, the need of sensitive methods, that could rapidly identify benzoylbenzofuran regioisomers, becomes crucial from this stand point, especially for 3-benzoyl-2-phenylbenzofurans containing nitro group, as they could provide convenient intermediates in the preparation of more complicated compounds. [10][11][12] In this study, we report the GC-MS n analyses of three series of isomeric mixture of benzoylbenzofurans obtained by Friedel-Crafts acylation of 2-phenylbenzofurans with benzoyl chlorides (Figure 1 and Scheme 1), aimed to distinguish and to identify, in the crude reaction mixtures, the 3-benzoyl isomers 1a-c from their 4-and 6-regioisomers 2a-c and 3ac, respectively. To this aim, multiple tandem mass experiments, performed in CID mode, were carried out using a quadrupole ion trap analyser (IT).…”

Multidirectional in vitro and in cellulo studies as a tool for identification of multi-target-directed ligands aiming at symptoms and causes of Alzheimer’s disease

“…The most explored multifunctional ligands combine anticholinesterase activity with anti-aggregation properties resulting from inhibition of β-secretase or modulation of γ-secretase and direct inhibition of processes of aggregation of Aβ and tau proteins 15–18 . Also, many G-protein coupled receptors are explored in combination with anticholinesterase activity, among them cannabinoid receptors CB 1 and CB 2 19–22 , histamine H 3 receptors 23–25 or serotonin 5-HT 1A 26 , 5-HT 4 , and 5-HT 6 receptors 27–31 .…”

Genetic factors related to the immune system in subjects at risk of developing Alzheimer's disease

“…Already the foremost cause of dementia and the sixth leading cause of death in the world, the impact of AD on health care systems is expected to rise owing to increasing global life expectancies (Montanari et al, 2019). Even so, symptomatic treatment currently constitutes the only therapy for AD (Montanari et al, 2019).…”

“…Already the foremost cause of dementia and the sixth leading cause of death in the world, the impact of AD on health care systems is expected to rise owing to increasing global life expectancies (Montanari et al, 2019). Even so, symptomatic treatment currently constitutes the only therapy for AD (Montanari et al, 2019). While experimental treatments for AD have been focused upon disturbing both pathogenic τ and Aβ protein aggregates, a stronger correlation has been found to exist between dementia and τ hyperphosphorylation than amyloid deposition (Arriagada et al, 1992;Sigurdsson, 2008).…”

“…Recently, immunomodulation via purposely designed pharmacologic has surfaced as a potential avenue in AD treatment, where benzofuran derivatives have been noted for their antiamyloidogenic, neuroprotective properties, mediated purportedly via cannabinoid receptor antagonism and butyrylcholinesterase inhibition (Montanari et al, 2019). Also, resveratrol has been identified as a modulator of neuroinflammation, promoting inter alia increased levels of the anti-inflammatory IL-4, decreased CSF matrix metalloproteinase 9, and inducing adaptive immunity (Moussa et al, 2017).…”