Anti-breast cancer potential analysis of phytochemicals in Selaginella doederleinii Hieron ethanolic extract through in silico study

Selaginella doederleinii Hieron has long been used traditionally by Indonesian to treat various diseases, including cancer. However, the anti-breast cancer activity of the plant has been little studied. This study aimed to identify the phytochemicals in Selaginella doederleinii Hieron extract and determine its anti-breast cancer potential, especially as PI3K/mTOR inhibitors using in silico approach. The phytochemicals were identified using LC-HRMS and analyzed for their physicochemical properties and potential anticancer activity through SwissADME, PASS prediction, and molecular docking. The LC-HRMS method tentatively identified 25 phytochemicals from the extract classified into four large groups. Among all these compounds, 14 compounds were predicted to possess good oral bioavailability and antineoplastic potential. Molecular docking studies showed that all compounds, except (6S,9R)Vomifoliol could interact with amino acid residues in the binding site of GDC-0326 in the PI3K p110a catalytic subunit. These compounds also had a comparable binding affinity with GDC-0326. Melosatin B, Bleekerine, and Affinisine had the lowest binding affinity scores and bound several residues interacting with the PI3K inhibitor. Meanwhile, all compounds could establish some chemical interactions with the binding site of Rapamycin in the FKBP51/FRB domain of mTOR, though they had a weaker binding affinity. Affinisine, Microhelenin C, and Alpinine had the lowest binding affinity scores and bound residues interacting with the mTOR inhibitor. Further in vitro and in vivo studies were required to validate the results.