In Silico Techniques Unveil the Anticancer Potential of Himalayan Pteridophytic Compounds via PI3K Inhibition

Introduction Inhibiting the signaling protein/gene involved in cancer progression may affect the signaling cascade and could be a possible targeted approach against progressive cancer. The present study aims to evaluate the anticancer potential of bioactive compounds from selected Himalayan pteridophytes by targeting the phosphoinositide 3 kinase (PI3K) pathway using in silico techniques. Materials and Methods In the present study, we identified various Himalayan pteridophytes via literature search from different search engines like Google Scholar, Science Direct, PubMed, etc. Among all, four Himalayan pteridophytes were chosen whose bioactive constituents were already identified by gas chromatography-mass spectrometry (GC-MS) analysis. Molecular docking via PyRx software was performed against two PI3K target proteins (PDB ID: 5OQ4and PDB ID: 3OAW) for determining the binding affinity of selected bioactive constituents against cancer. Drug likeliness and toxicity assessment were also carried out by using Swiss ADME and ProTox-II. Results and Discussion Molecular docking study identified 12 bioactive molecules with favorable binding affinities (ranging from -7.3 to -10.00 kcal/mol) against PI3K pathway. Among 12 constituents, 3 molecules named as PC-2 (Matteucinol), PC-4 (Matteuorienate-A), and PC-9 (flavan-4-ol) have binding affinity more than the reference compounds. These results suggest that these constituents may serve as a promising candidate for further in vitro and in vivo studies in cancer therapeutics. The selected bioactive compounds demonstrate promising anticancer activity via PI3K inhibition, warranting further experimental validation and development as potential cancer therapeutics.