Potential cervical anticancer activity of tomcat beetle (Paederus fuscipes) compounds against estrogen alpha receptor (3ert): In silico study

Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Daerah Istimewa Yogyakarta, Indonesia

^* Corresponding author: dwi.utami@pharm.uad.ac.id

Abstract

Cervical cancer is at the top of the list of women’s gynecologic cancers in developing countries. Various compounds have been developed to fight cancer, but none of these compounds cause satisfactory effects. Much research has been done on anticancer drug ingredients from nature. The tomcat beetle (Paederus fuscipes) contains pederin, pseudopederin, and pederone toxins, which are suspected to have interactions and ADMET profiles against ERα receptors (3ERT) compared to the anti-cancer drugs genistein and tamoxifen. The research includes preparation, RMSD method validation, molecular docking, PreADMET, and visualization. Data were analyzed by comparing bond energy, type of bond, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity). The results obtained were the bond energies of tamoxifen -10.68 kcal/mol, genistein -7.87 kcal/mol, pederin -7.57 kcal/mol, pseudopederin -8.07 kcal/mol, and pederone -7.83 kcal/mol. The compound from the tomcat beetle with the lowest bond energy is pseudopederin. Amino acid residue interactions in P. fuscipes compounds have similarities with tamoxifen, and genistein mechanism as SERMs (selective estrogen receptor modulators). In PreADMET study, results showed that genistein, compared to tamoxifen, has more toxic effects than compounds from P. fuscipes. As conclusion, the compounds in P. fuscipes have the potential to be developed as a candidate for anticancer agents through inhibition of the alpha estrogen receptor (3ERT) based on in silico study.