In vitro cytotoxic effects, in silico studies, some metabolic enzymes inhibition, and vibrational spectral analysis of novel β-amino alcohol compounds

Abstract

In this study, an efficient single-step method for the preparation of β-amino alcohols (1–3) in aqueous media was applied. The aim was to investigate the cytotoxic activity of Compounds 1, 2 and 3 in neuroblastoma SH-SY5Y cell line and mouse fibroblast l-929 cell lines. Cytotoxic activities of compounds 1, 2 and 3 in this cell lines were also determined by MTT method. Cells were incubated with different concentrations of Compound 3 showed the highest cytotoxic activity in SHY5Y cells at an IC50 dose of 13.01±0.87 µM at 72 h compared to other compounds. Compound 3 was determined to have lower cytotoxic activity in l-929 cells. The chemical activities of the molecules against the B3LYP, HF, M062X level 3–21 g, 6–31 g, and SDD basis set with the Gaussian package program and biologically against the adenosine A(2A) receptor (PDB ID: 3PWH and 5NM4) proteins for neuroblastoma tumors cell with the Maestro Molecular modeling platform by Schrödinger were compared. Both experimental and theoretical NMR, UV–vis, and IR spectra of the studied molecules were compared. ADME/T analysis was performed to examine the drug properties of the molecules. Finally, these assayed for their activities against metabolic enzymes acetylcholinesterase and α-glucosidase. The most potent compounds against AChE were order compounds 3, 2 and 1 with Ki values of 35.88±6.61, 43.75±8.28, and 45.34±3.50 µM against AChE, respectively. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. These inhibitors may be candidates for drug design.