In Silico Screening of Annona Metabolites Against CYP17A1 and β-tubulin Using PLANTS Docking

Didik Rio Pambudi; Hafiz Ramadhan; Citra Kharisma Dewi

doi:10.37311/jsscr.v8i1.33360

In Silico Screening of Annona Metabolites Against CYP17A1 and β-tubulin Using PLANTS Docking

Didik Rio Pambudi, Hafiz Ramadhan, Citra Kharisma Dewi

Abstract

Prostate cancer progression is closely associated with androgen biosynthesis mediated by cytochrome P450 17A1 (CYP17A1) and with microtubule dynamics regulated by β-tubulin, making both proteins important therapeutic targets. The Annona genus is a rich source of acetogenins with reported anticancer potential; however, their interactions with prostate cancer–related targets remain insufficiently explored. In this study, an in silico exploratory approach was employed to evaluate 30 Annona-derived compounds against CYP17A1 (PDB ID: 3RUK) and β-tubulin (PDB ID: 1JFF) using the PLANTS (v1.1) molecular docking program. Docking protocol validation was based on RMSD values ≤ 2 Å, and compound prioritization was performed using docking scores and binding-site residue similarity relative to native ligands and reference drugs. The docking results identified squafosacin-C as the top-ranked compound for both targets, exhibiting docking scores of −133.289 for CYP17A1 and −131.825 for β-tubulin. These values were more favorable than those of the native ligands (−82.5591 and −103.071) and the reference drugs abiraterone and docetaxel (−83.6465 and −99.7319, respectively). Visualization analysis further revealed that squafosacin-C shares 7 of 8 key amino acid residues involved in native ligand binding at both targets, indicating a conserved binding mode. In conclusion, based on molecular docking and interaction analysis, squafosacin-C emerges as a promising lead compound at the computational level for targeting CYP17A1 and β-tubulin in prostate cancer. These findings provide a rationale for further investigation through molecular dynamics simulations and experimental validation to confirm its biological activity.

Keywords

Molecuular docking; PLANTS; Prostate cancer; Annona; Acetogenins

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DOI: https://doi.org/10.37311/jsscr.v8i1.33360

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