Structure-based virtual screening of anti-breast cancer compounds from Artemisia absinthium—insights through molecular docking, pharmacokinetics, and molecular dynamic simulations

Abstract

Breast cancer is the world’s second most frequent malignancy, with a significant mortality and morbidity rate. Nowadays, natural breast cancer medicine has piqued attention as disease-curing agent with low side effects. Herein, the leaf powder of Artemisia absinthium was extracted with ethanol, and GC-MS and LC-MS methods were employed to identify the phytocompounds. Using commercial software SeeSAR-9.2 and StarDrop, identified phytocompounds were docked with estrogen and progesterone breast cancer receptors as they promote breast cancer growth to find the binding affinity of the ligands, drugability, and toxicity. Hormone-mediated breast cancer accounts for about 80% of all cases of breast cancer. Cancer cells proliferate when estrogen and progesterone hormones are attached to these receptors. The molecular docking results demonstrated that 3’,4’,5,7-Tetrahydroxyisoflavanone (THIF) has stronger binding efficacy than standard drugs and other phytocompounds with −28.71 (3 hydrogen bonds) and −24.18 kcal/mol (6 hydrogen bonds) binding energies for estrogen and progesterone receptors, respectively. Pharmacokinetics and toxicity analysis were done to predict the drug-likeness of THIF which results in good drugability and less toxicity. The best fit THIF was subjected to a molecular dynamics simulation analysis by using Gromacs to analyze the conformational changes that occurred during protein-ligand interaction and found that, the structural changes were observed. The results from MD simulation and pharmacokinetic studies suggested that THIF can be expected that in vitro and in vivo research on this compound may lead to the development of a potent anti-breast cancer drug in the future. Communicated by Ramaswamy H. Sarma