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2000
Volume 21, Issue 6
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

Introduction

Liver cancer is considered one of the most common types of cancer and a major cause of ephemerality worldwide having a higher prevalence rate in Asia and sub-Saharan Africa. The alpha-fetoprotein (AFP) is a serum glycoprotein that belongs to a class of onco-developmental proteins and is also involved in tumor formation.

Methods

In the current effort, a hybrid approach of virtual screening followed by pharmacophore generation and molecular dynamic simulation analyses were performed. The screened top-ranked 10 docked compounds from the selected anti-cancer compound library were utilized to generate the ligand-based pharmacophore. Virtual screening was performed two-dimensional similarity search against the selected natural compound library based on their physicochemical properties. It was observed that all the compounds from the anti-cancer compound library and natural compound library showed similar binding resides.

Results

Therefore, the top-ranked screened compounds that showed the least binding energy and highest binding affinity against AFP, obtained through the anti-cancer drug library and natural compound library were reported. The molecular docking analyses revealed that Leu-219, His-222, Lys-242, Lys-246, His-316, Glu-318, Ala-366, Val-367, Gly-475, Ile-479, Ala-471, Asp-478 were observed as potential residues for interaction.

Conclusion

The observed results of virtual screening, molecular docking, and MD simulation analyses entail noteworthy observations illustrating that NC002 was a potent inhibitor. The proposed compound NC002 may have potential against liver cancer by targeting AFP based on MD simulation analyses, PCA, and MM-GBSA.

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In silico Identification and Computational Screening of Potential AFP Inhibitors Against Liver Cancer
Med. Chem. 21, 554 (2025); https://doi.org/10.2174/0115734064330103250106034126
/content/journals/mc/10.2174/0115734064330103250106034126
/content/journals/mc/10.2174/0115734064330103250106034126
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  • Article Type:     Research Article
Keyword(s): anti-cancer compound; anti-cancer drug; Computational screening; inhibitors; liver cancer; pharmacophore; potential AFP

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