Design, synthesis, in-silico, and in-vitro assessment of pyrazolone-merged chalcone derivatives as anti-alzheimer agents
DOI:
https://doi.org/10.1590/s2175-97902025e24291Keywords:
Anti-cholinesterase, (E)-2-(4-chlorobenzoyl)-5-(2-fluorostyryl)-2,4-dihydro-3Hpyrazol- 3-one, Molecular docking, Human SH-SY5Y neuroblastomacelllines, ADMETAbstract
Novel anti-cholinesterase inhibitors including pyrazolone merging chalcone derivatives have been developed and molecular docking has been performed. From the docking results, compound 48 (-8.3 k/cal) shows the highest binding affinity toward the AChE enzyme compared to the standard drug donepezil (-12.76k/cal). This compound produced two conventional hydrogen bonds between the carbonyl oxygen and residue of Asn 491. Every synthetic chemical underwent screening to determine its ability to cause in vitro cytotoxicity activity against Human SH-SY5Y neuroblastoma cell lines. The cells of SH-SY5Y were preincubated for 30 minutes with varying doses of the chosen compounds like 8, 9, 10, 11, 31, 37, 44, 47, 48, and 50 to induce neurotoxicity. They were then grown in Aβ25-35 (25 mol/L) for 48 hr. Cell viability was determined by MTT assay. Compounds 8, 11, and 48 exhibited a better binding score -8.2k/cal -8.2k/cal and -8.3k/cal respectively compared to other analogs. Synthesized compounds 8, 11, and 48 inhibited Aβ25-35-induced apoptosis in SH-SY5Y cells and protected neural cells from damage. The MTT assay confirmed compound 48 significantly reduced Aβ25-35-induced toxicity among human neuroblastoma SH-SY5Y cells, demonstrating its neuroprotective properties.
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