Molecular docking studies of biflavonoids from Selaginella doederleinii hieron as anticancer agents to inhibit mTOR

The mammalian/mechanistic target of rapamycin (mTOR) is a serine/threonine kinase which commonly hyperactivated in the majority of cancers. mTOR was reportedly involved in various tumorigenesis and cancer development. Cancer therapy, combined with mTOR inhibitors, can be a good strategy for cancer treatment. Biflavonoids from Selaginella doederleinii Hieron are known to possess anticancer activity. Therefore, this study aimed to investigate the potency of the biflavonoids to inhibit mTOR via rapamycin and ATP-binding sites and determine oncogenic proteins that interacted with mTOR. The research methods were molecular docking and protein interaction network analysis. All compounds had lower binding affinities than rapamycin, a native inhibitor of mTOR in the rapamycin-binding site. However, all compounds could bind mTOR in the same site as rapamycin and had several amino acid residues similarities with rapamycin. Meanwhile, 3′,3″′-binaringenin was the only compound that had the same binding position as PP242, a native ligand of the ATP-binding site of mTOR. The compound also had a higher binding affinity than PP242 and some similarities of amino acid residues with it. mTOR could interact with RAPTOR, RICTOR, MAPKPA1, Rheb, RPS6KB1, EIF4EBP1, LAMTOR1, LAMTOR2, LAMTOR4, and LAMTOR5. Nonetheless, this research still needs further studies to validate the in-silico results.