Theviridoside, Alcesefoliside, and Cycloolivil as natural compounds: Discovery of new HMG-CoA reductase, alpha glucosidase inhibitors and anti-gastric potential

One of the deadliest and most prevalent cancers in the world is gastric cancer, also known as stomach cancer. According to GLOBOCAN 2018 data, stomach cancer ranks third globally in terms of cancer mortality, behind colorectal and lung cancer. Gastric cancer is the fifth most prevalent type of cancer overall. Gastric cancer is one of the most well-known and dangerous tumors, with a poor prognosis and a high total mortality rate from malignant progression. Additionally, Alpha-glucosidase inhibitors are widely used oral antidiabetic medications that regulate the breakdown of carbohydrates into simple sugars that the intestines can absorb. HMG CoA reductase and α-glucosidase were inhibited in this study by Theviridoside, Alcesefoliside, and Cycloolivil molecules, with IC50 values of 1.70±0.03 and 26.71±1.04 µM for Theviridoside, 0.98±0.01 and 4.35±0.06 µM for Alcesefoliside, and 6.27±0.02 and 41.20±0.87 µM for Cycloolivil, respectively. The anti-cancer properties of the compounds were assessed using the SNU1 (IC50: 65.32 ± 2.70, 76.31 ± 1.44 and 20.52 ± 1.25 µM), AGS (IC50: 61.35±2.73, 89.46±1.06 and 11.76±0.63 µM), and MKN45 (IC50: 56.71±0.98, 83.50±2.62 and 14.87±1.12 µM) cell lines, respectively. The binding affinity and interactions of theviridoside, alcesefoliside, and cycloolivil against HMG-CoA reductase and α-glucosidase were assessed by using computational methods such as MM/GBSA calculations, molecular modeling, and molecular dynamics (MD) simulations. Moreover, their activity against three gastric cancer cell lines, SNU1, AGS, and MKN45 was evaluated. Their interactions and affinities with multiple surface receptor proteins, such as CD44, estrogen receptor, and EGFR, were investigated using computational methods. Based on the results, these compounds can form strong interactions with the target enzymes and receptors. Therefore, Alcesefoliside, theviridoside, and cycloolivil can effectively inhibit the activity of these enzymes and cancer cell lines.