Inhibition of Beta‐Amyloid Peptide Aggregation by Multifunctional Carbazole‐Based Fluorophores

Biological potential of carbazole derivatives

“…One of the widely accepted theories says that beta-amyloid (Ab) peptides of 40 and 42 residues (Ab 42 are more prone to aggregate than Ab 40 or Ab 38 ) formed from the cleavage of amyloid precursor protein play a key role in AD pathogenesis [39,40]. The aggregation of monomeric Ab peptides to insoluble plaque also known as senile plaques may lead to the death of neuronal cells (on microscopic level plaques accumulate on the walls of blood vessels).…”

“…The g-secretase complex catalyzes the most important step in the liberation of these Ab isoforms, and this can be a promising target for prevention of AD [39]. In recent years effective fibril inhibitors and b-sheet breakers that can prevent the aggregation of Ab monomers into oligomeric and fibrillar conformations have been developed [40]. The tested compounds must show bloodebrain barrier (BBB) permeability, low neurotoxicity and high in vivo stability to be clinically useful.…”

“…One of the compounds that can penetrate the bloodebrain barrier, which makes it a potential neuroprotective and/or therapeutic agent for Alzheimer's disease, is SLOH 22d [40]. It was shown to inhibit the aggregation of Ab peptides and oligomers, thus preventing the fibril growth.…”

Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents

“…Thus, inhibition of the Ab aggregation has been presented as a promising approach for the development of anti-AD agents. It was reported previously that carbazole and benzofuran scaffolds had ability to inhibit Ab aggregation [5,23]. In order to investigate the inhibitory effect of the synthesized analogs on Ab aggregation, compound 3 (5, 50, 100 mM), which showed good activity in all former tests, and galantamine (5, 50, 100 mM) were selected to perform Thioflavin T (ThT) assay.…”

“…Nevertheless, as mentioned above, AD is a multifactorial disease, and traditional AChEIs like tacrine and donepezil can only hit AChE one target without influence on other pathogenic factors of AD, especially Ab and its aggregates which play a key role in triggering a neurotoxic cascade and have been considered as a primary target for developing novel anti-AD candidates (e.g. carbazolebased fluorophores [5] and bifunctional metal chelators [6]). Thereby, AChEIs can offer only a palliative effect, but not halt the progression of the disease.…”