5-O-Acetylpinostrobin derivatives as estrogen-α inhibitors: Molecular docking and pharmacokinetic analysis

Estrogen receptor alpha (ER-α) is an attractive and important target in breast cancer tissue development and a trigger for carcinogenesis. More than 70–75% of most breast cancers are ER-α. However, due to problems with ER-α inhibitors as major challenges related to intrinsic resistance, recurrent metastasis, additive effects, and estradiol antagonists, it’s necessary to identify new effective and selective inhibitor compounds. The aim of this study was to predict the anticancer activity, pharmacokinetics, and toxicity of twenty 5-O-acetylpinostrobin derivatives. The method used for activity prediction was the molecular docking approach with the Molegro Virtual Docker. While pharmacokinetics and toxicity (ADMET) studies with pkCSM online. The results of the molecular docking study showed a rerank score value of twenty 5-O-acetylpinostrobin derivatives of -113.8310 to -71.7388 kcal/mol. Eight compounds (AP-10-12, 14-16, and 19-20) had a smaller rerank score than pinostrobin and native ligand. The similarity of amino acid residue interactions such as a donor hydrogen bond between the oxygen atom of the chroman-4-on ring and Arg 394 as well as a steric interaction between Glu 353 and the C-aromatic of the chroman-4-on ring. The results of pharmacokinetics and toxicity studies showed that all compounds derived from 5-O-acetylpinostrobin have good absorption, distribution, metabolism, and excretion, as well as low toxicity. The conclusion of this study was that compound codes AP-10, 11, 14, 15, 19, and 20 have greater predicted breast anticancer activity, better pharmacokinetics, and lower toxicity than pinostrobin and 4-hydroxytamoxifen. Therefore, these six compounds have the potential to be developed further.