The current research discusses the loaded of F3S4-m compound reported with multitarget activity acting as an inhibitor of acetylcholinesterase (AChE), beta-secretase 1 (BACE1), and amyloid beta (Aβ) aggregation. Despite great effort has been done to have a compound to treat Alzheimer’s disease (AD) and not only its symptomatology, nowadays there is not an effective compound in the market yet. Several synthetized compounds reported having a good activity in vitro study turned out not having it in vivo, it is believed that many of them are not able to reach the brain due to low biodisponibility, besides many of them have charged chemicals groups or tertiary amines, which have been substrates of deaminases enzymes. Therefore, the use of liposomes results an interesting strategy to deliver this kind of compounds to the brain. Then in this work it is proposed the use flexible liposomes made from phosphatidylcholine (PC) and cholesterol (Chol) to encapsulate the F3S4-m compound and evaluate its inhibitory activity against AChE. The results showed that empty liposomes particle size is influenced by the content of cholesterol in their membranes being larger for those containing 20% of cholesterol than those with 10%. The toxicity of F3S4-m loaded liposomes in PC12 cells was also evaluated employing the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay (MTT). The results showed that F3S4-m loaded liposomes can inhibit the enzymatic activity of AChE, but the concentration of encapsulated F3S4-m needed to inhibit AChE was 2-times higher than what was previously reported in solution. Graphical abstract

Alzheimer’s disease (AD) is a neurodegenerative disease with no cure nowadays; there is no treatment either to prevent or to stop its progression. In vitro studies suggested that tert-butyl-(4-hydroxy-3-((3-(2-methylpiperidin-yl)propyl)carbamoyl)phenyl) carbamate named the M4 compound can act as both β-secretase and an acetylcholinesterase inhibitor, preventing the amyloid beta peptide (Aβ) aggregation and the formation of fibrils (fAβ) from Aβ_1-42. This work first aimed to assess in in vitro studies to see whether the death of astrocyte cells promoted by Aβ_1-42 could be prevented. Second, our work investigated the ability of the M4 compound to inhibit amyloidogenesis using an in vivo model after scopolamine administration. The results showed that M4 possesses a moderate protective effect in astrocytes against Aβ_1-42 due to a reduction in the TNF-α and free radicals observed in cell cultures. In the in vivo studies, however, no significant effect of M4 was observed in comparison with a galantamine model employed in rats, in which case this outcome was attributed to the bioavailability of M4 in the brain of the rats.

Amyloid beta (Aβ) is a key biomarker in Alzheimer’s disease, driving the formation of senile plaques that contribute to neuronal death within a complex etiology. Typically, most treatments begin at advanced stages, when irreversible brain atrophy has already occurred; therefore, early diagnosis is essential for effective intervention. Several probes based on the conventional donor−π–acceptor (D−π–A) structural motif have been developed as diagnostic tools, yet few have reached clinical trials. Alternatively, quinoline-based fluorescent compounds with push–pull structures and aggregation-induced emission properties show enhanced fluorescence in the aggregated state due to restricted intramolecular motion (RIM). Accordingly, four quinoline derivatives2QnCN, 3QnCN, 3QnB, and 4QnBBwere synthesized using standard methods, including benzoxazole segments and a cyano (−CN) group. They were chemically and optically characterized, and their photophysical properties were calculated. Theoretical analyses include band gap estimation and visualization of intramolecular charge transfer. Molecular docking was also performed to assess binding with the Aβ_1–42 pentamer (PDB: 2BEG), identifying 3QnCN as the most promising candidate with a binding energy of–11.9 kcal/mol. Cytotoxicity was tested using the MTT assay to determine the optimal working concentration. The fluorescence intensity of 3QnCN in PC12 cells was quantified, and confocal microscopy confirmed its effectiveness in labeling Aβ_1–42.