Screening Saffron-Derived Apocarotenoids Against NUDT1 in Hepatocellular Carcinoma: An Integrated Computational Study

Authors

  • Nethraa Kannan University College Dublin, Ireland Author
  • Pernilla Siljehag Karolinska Institutet, Sweden Author
  • Hager Saleh Karolinska Institutet, Sweden Author

Keywords:

Crocus sativus, crocin, crocetin, NUDT1, hepatocellular carcinoma, docking

Abstract

Background: Saffron contains apocarotenoids with reported antioxidant, anti-inflammatory and anticancer activity, yet their interactions with oxidative-nucleotide defence proteins remain incompletely explored.

Objective: To evaluate saffron-derived metabolites as potential NUDT1 ligands in hepatocellular carcinoma.

Methods: Twenty-seven reported saffron constituents and metabolites were curated, geometry-optimised and screened against NUDT1. Drug-likeness, predicted metabolism and off-target liabilities were assessed before 100-ns simulations of the three strongest complexes.

Results: Crocetin, picrocrocin metabolite PM-4 and safranal analogue SA-2 achieved docking scores below -8.0 kcal/mol. Crocetin formed a stable hydrogen-bond network near the catalytic pocket and maintained an average ligand RMSD of 1.84±0.27 Å. Its mean MM/GBSA energy was -31.6±4.9 kcal/mol. PM-4 showed slightly weaker binding but superior predicted solubility. Crocin itself was penalised by size and polarity despite favourable contact density. Network mapping of predicted secondary targets connected the leading compounds to oxidative-stress response, apoptosis and inflammatory signalling. No candidate generated high-confidence mutagenicity alerts, although crocetin and SA-2 showed potential CYP interactions that would require experimental verification.

Conclusion: Saffron-derived metabolites demonstrated plausible computational affinity for NUDT1, with crocetin emerging as the strongest candidate for enzyme-based validation. The findings connect phytochemical pharmacology with oxidative-nucleotide biology and provide a testable framework for investigating whether saffron metabolites can influence cancer-cell redox adaptation.

Publication format: research abstract. No full-text manuscript accompanies this record.

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Published

2026-10-01

Issue

Vol. 1 No. 1 (2026): October 2026 — Inaugural Issue

Section

Research Papers

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Copyright (c) 2026 Zofia Kowalska, Yousef Haddad, Rizky Pratama

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