In silico and in vitro study of bioactive compounds from Allium sativum with PTEN: A novel target and promising source for cancer diagnostic potentials

Abstract

Introduction: Cancer remains a significant global health issue, necessitating innovative management strategies. The tumor suppressor protein PTEN, due to its pivotal role in cancer development, is a promising target for therapeutic intervention. Materials and Methods: We used dried Allium sativum (garlic) seed extract to discover phytocompounds that could inhibit PTEN in cancer. We conducted qualitative tests to determine the phytochemical composition of the extract and employed a DPPH radical scavenging assay to evaluate its antioxidant activity. Computational methods were used to explore the impact of Allium sativum and its constituents on PTEN. This involved predicting and validating 3D structures using the SWISS model and ITASSER, performing docking analysis with natural compounds from the Asinex database, and assessing the drug-likeness and ADMET characteristics of selected compounds using online tools. Molecular dynamics simulations (MDS) were conducted to examine protein–ligand interactions, and the results were analyzed to understand complex stability and fluctuations. Results: A study on Allium sativum revealed the presence of diverse phytochemicals in its seeds and leaves. The leaves contained alkaloids and saponins, while the methanol extract of the leaves exhibited the highest flavonoid and phenolic contents. This methanol extract demonstrated potent antioxidant activity and significantly inhibited cytotoxicity. Through computer-aided drug design, we identified potential anticancer drugs derived from natural botanicals that target the PTEN protein. The virtual screening process led to the discovery of three lead compounds exhibiting high binding affinities and interactions with PTEN. Molecular docking and MDS indicated the strong binding energy and favorable drug-like properties of these compounds. While the protein exhibited some flexibility, the ligand–protein complex remained stable. Conclusion: This study contributes to the expanding literature on cancer drug discovery and emphasizes the importance of investigating natural plant compounds in the search for novel and effective cancer treatments.

Keywords

• Anti-Cancer Compounds
• Allium sativum
• PTEN
• Cancer
• Bioinformatics