In silico study: Proposed Natural Compounds Inhibitor of ALDH1A1 for 288 the Possible Therapeutic Potential as an Anti-Ovarian Cancer Stem Cells

Abstract

According to American Cancer Society, cancer becomes the second biggest cause of death in the world after heart disease and ovarian cancer is one of the leading causes of death among other women cancers. Ovarian cancer is ranked third of the most common gynecological cancer. In the last decade, many studies have been focused on targeting cancer stem cells as another way to treat cancer. Cancer stem cells are suspected to be the cause of chemoresistant and cancer recurrence. Aldehyde Dehydrogenase 1 Family Member A1 (ALDH1A1) is a novel inhibitor target and known to be a functional marker of ovarian cancer stem cells. The purpose of this research is to find an active compound that potential to be an inhibitor for ALDH1A1. This research has been conducted by examined the binding affinity between receptor and active compounds using Autodock Vina. These active compounds were assessed for bioavailability and pharmacokinetics as a drug candidate. Visualization of interactions between molecules has been done in 2D visualization to get an optimum view. The results showed that there were five active compounds with lower binding affinity than the inhibitor as a control ligand. The binding affinity of these ligands were -11.5 kcal/mol, -10.8 kcal/mol, 10.3 kcal/mol, -10.1 kcal/mol and -9.9 kcal/mol with -9.6 kcal/mol for CM053 as the inhibitor. Phe171, Cys302 and Gly458 are essential residues for binding site. Benzo[e][1]benzothiopyrano[4_3_b]indole, gartanin, mangostinone, smeathxanthone A and Garcinone A from mangosteen shows potency as a drug candidate by targeting ALDH1A1 inhibition.