Structure-Based Virtual Screening of Nigella sativa Compounds as Potential Anti-Lung Cancer Agents Targeting PI3Kα

Background: Lung cancer (LC) is one of the deadliest tumors. Hyperactivation of phosphatidylinositol 3-kinase (PI3K) has been linked to cancer etiology.Methods: This study computationally screens the Nigella sativa compounds and their interactions with PI3Kα to identify potential therapeutic agents for LC. Copanlisib was chosen as the positive control for virtual screening. The LOTUS database was used to produce a library of 132 compounds that represent bioactive components of N. sativa. Molecular properties and molecular descriptors of N. sativa compounds were obtained from the LOTUS database.Results: Compounds were ranked based on their binding energy to PI3Kα and interactions with key residues in the PI3Kα binding pocket. The screening identified five compounds as top hits: LTS0117717, LTS0169227, LTS0183019, LTS0241372, and LTS0249588, which had stronger binding energy than the control Copanlisib. LTS0117717, LTS0169227, LTS0183019, LTS0241372, and LTS0249588 had binding energies of -9.8, -9.6, -9.5, -9.1, and -9.0 kcal/mol, respectively, while the Copanlisib (control) had a binding energy of -8.6 kcal/mol. These compounds interacted with active site residues of PI3Kα. In addition, these compounds have good druglike properties.Conclusion: The compounds LTS0117717, LTS0169227, LTS0183019, LTS0241372, and LTS0249588 can be used as PI3Kα inhibitors to treat the LC. However, further experimental studies are warranted to validate these compounds as PI3Kα inhibitors.Keywords: Lung cancer; PI3Kα; Nigella sativa; Drug likeness