Natural Compounds from Alhagi maurorum as Potential HCC and HepG2 Inhibitors: An Integrated Study using Pharmacophore Development, Molecular Docking, MD Simulation, and DFT Approaches

Aniqa Moveed; Shagufta Parveen; Nusrat Shafiq; Awais Ali; Maryam Rashid; Mohammed Bourhia; Fouad Msanda; Ahmad Mohammad Salamatullah; Simone Brogi

doi:10.2174/0115734064309469240806104435

Natural Compounds from Alhagi maurorum as Potential HCC and HepG2 Inhibitors: An Integrated Study using Pharmacophore Development, Molecular Docking, MD Simulation, and DFT Approaches

Med Chem. 2025 Jan 20. doi: 10.2174/0115734064309469240806104435. Online ahead of print.

Authors

Aniqa Moveed¹, Shagufta Parveen¹, Nusrat Shafiq¹, Awais Ali², Maryam Rashid¹, Mohammed Bourhia³, Fouad Msanda³, Ahmad Mohammad Salamatullah⁴, Simone Brogi⁵

Affiliations

¹ Synthetic and Natural Product Drug Discovery Laboratory, Department of Chemistry, Government College Women University Faisalabad-38000, Pakistan.
² Department of Biochemistry, Abdul wali Khan University Mardan, Pakistan.
³ Laboratory of Biotechnology and Natural Resources Valorization, Faculty of Sciences of Agadir, Ibn Zohr University, Agadir, Morocco.
⁴ Department of Food Science & Nutrition, College of Food and Agricultural Sciences, King Saud University, 11 P.O. Box 2460, Riyadh 11451, Saudi Arabia.
⁵ Department of Pharmacy, Pisa University, Pisa, Italy.

PMID: 39838657
DOI: 10.2174/0115734064309469240806104435

Abstract

Background: The rise in the frequency of liver cancer all over the world makes it a prominent area of research in the discovery of new drugs or repurposing of existing drugs.

Methods: This article describes the pharmacophore-based structure-activity relationship (3DQSAR) on the secondary metabolites of Alhagi maurorum to inhibit human liver cancer cell lines Hepatocellular carcinoma (HCC) and hepatoma G2 (HepG2) which represents the molecular level understanding for isolated phytochemicals of Alhagi maurorum. The definite features, such as hydrophobic regions, average shape, and active compounds' electrostatic patterns, were mapped to screen phytochemicals. The 3D-QSAR model generates pharmacophore-based descriptors and alignment of active compounds. Further, docking studies were performed on the active compounds to check out their binding affinity with the active site of the target proteins. It was further validated by applying molecular simulations, and the results were found to be accurate. The geometrical optimization and energy gap of the hit compound were calculated by the density functional theory (DFT). Then, ADMET was performed on this hit compound for drug-like features and toxicity.

Result: Out of 59 compounds, eight ligands were found active after the 3D-QSAR study. After that, molecular docking was performed on the active compounds F72, F52, F54, F29, F37, F38, F25, and F29, which were recognized as potential targets, and the docking results showed that compound F52 (also an FDA-approved drug) was the best hit. F52 was found to be the best hit against liver cancer cell lines HCC and HepG2.

Conclusion: This study would be helpful for early drug discovery optimization and lead identification.

Keywords: Hepatocellular; carcinoma; hepatoblastoma cell line; malignant tumor.; molecular electrostatic potential; structure-activity relationship.