%0 Journal Article
%T Study of potential inhibition of the estrogen receptor α by cannabinoids using an in silico approach: Agonist vs antagonist mechanism.
%A Rocha-Roa C
%A Cortes E
%A Cuesta SA
%A Mora JR
%A Paz JL
%A Flores-Sumoza M
%A Márquez EA
%J Comput Biol Med
%V 152
%N 0
%D 01 2023
%M 36543006
%F 6.698
%R 10.1016/j.compbiomed.2022.106403
%X Breast cancer is the main cancer type with more than 2.2 million cases in 2020, and is the principal cause of death in women; with 685000 deaths in 2020 worldwide. The estrogen receptor is involved at least in 70% of breast cancer diagnoses, and the agonist and antagonist properties of the drug in this receptor play a pivotal role in the control of this illness. This work evaluated the agonist and antagonist mechanisms of 30 cannabinoids by employing molecular docking and dynamic simulations. Compounds with docking scores < -8 kcal/mol were analyzed by molecular dynamic simulation at 300 ns, and relevant insights are given about the protein's structural changes, centered on the helicity in alpha-helices H3, H8, H11, and H12. Cannabicitran was the cannabinoid that presented the best relative binding-free energy (-34.96 kcal/mol), and based on rational modification, we found a new natural-based compound with relative binding-free energy (-44.83 kcal/mol) better than the controls hydroxytamoxifen and acolbifen. Structure modifications that could increase biological activity are suggested.