In Vitro Cytotoxicity Evaluation and Bioactivity Effects of 5-O-Methylnaringenin and 7-Methylrosmanol as Natural Compounds: A Biochemical Approach

The aim of this study was to investigate the enzyme inhibitory and anticancer effects of two natural compounds, 5-O-Methylnaringenin and 7-Methylrosmanol, on HMG-CoA reductase, monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B), as well as their effects on gastric cancer cell lines. The enzyme responsible for producing cholesterol in the mevalonate pathway is 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. The liver produces less cholesterol when HMG-CoA reductase is inhibited. Statins are synthetic medications that are frequently used to treat high cholesterol. Statin side effects necessitate the use of natural plant-based HMG-CoA reductase inhibitors. In this study, 5-O-Methylnaringenin and 7-Methylrosmanol molecules inhibited the enzymes HMG CoA reductase, monoamine oxidase A and B, with IC50 values of 31.60 ± 0.42, 24.74 ± 0.64, and 51.86 ± 0.90 µM for 5-O-Methylnaringenin and 14.86 ± 0.40, 176.24 ± 2.86 and 124.53 ± 1.47 µM for 7-Methylrosmanol. The NCI-N87 (IC50: 8.70 ± 0.15 and 23.68 ± 1.08 µM) and MKN45 (IC50: 6.63 ± 0.10 and 17.36 ± 0.87 µM) cell lines were used to evaluate the compounds' anti-cancer capabilities, respectively. The biological impacts of 5-O-Methylnaringenin and 7-Methylrosmanol on HMG-CoA reductase, MAO-A, and MAO-B were assessed through various methodologies, including molecular modeling studies, MM/GBSA calculations, and molecular dynamics simulations. Furthermore, the anti-cancer effects of these compounds were evaluated against two gastric cancer cell lines, NCI-N87 and MKN45. The chemical interactions of these compounds with multiple surface receptor proteins, such as CD44 and EGFR, were investigated using computational methods. The results indicated significant interactions at the atomic level, suggesting that the compounds formed robust connections with certain enzymes and receptors. 5-O-Methylnaringenin and 7-Methylrosmanol exhibit the potential to inhibit the activity of these metabolic enzymes and hinder the proliferation of cancerous cells.