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This research evaluates the potential interactions of soursop leaf compounds with the CYP450 enzyme system.

April 21, 2026Open Access

In Silico Evaluation of Soursop (Annona muricata) Leaf Compound Interactions with CYP450 and Their Potential Impact on Systemic Cancer Therapies

Key Points

This research evaluates the potential interactions of soursop leaf compounds with the CYP450 enzyme system.
Used SuperCYPsPred and SwissADME platforms to analyze 12 leaf compounds from A. muricata.
Identified interaction probabilities and pharmacokinetic characteristics of compounds, focusing on CYP2D6.
Performed risk assessment to categorize compounds based on their interaction potential.
Aporphine alkaloids were found to exhibit high CYP2D6 interaction probabilities between 55.9% and 94.9%.
Four compounds identified as high-risk for drug interactions during chemotherapy.
Acetogenins were shown to have low oral bioavailability, indicating lower interaction risk than other compounds.

Abstract

Annona muricata (soursop, graviola) is a tropical plant widely used in traditional medicine for the management of various ailments, including cancer. Its leaf and fruit extracts are frequently consumed as complementary therapies by oncology patients, yet their potential to interfere with CYP450-mediated drug metabolism remains poorly characterized. This study employed two complementary in silico platforms, SuperCYPsPred for CYP450 interaction probability predictions and SwissADME for ADME/pharmacokinetic profiling, to evaluate 12 representative leaf compounds, as leaves constitute the most used plant part in traditional medicinal preparations of A. muricata . SuperCYPsPred analysis identified aporphine alkaloids as having the highest predicted interaction probabilities: isolaureline (mean 61.5%), xylopine (59.9%), and anonaine (55.9%), with particularly high CYP2D6-specific probabilities (94.9%, 88.8%, and 85.7%, respectively). SwissADME analysis revealed that these same compounds exhibit high gastrointestinal absorption, blood-brain barrier permeability, favorable drug-likeness, and predicted CYP2D6 inhibition. Integrated risk assessment combining both platforms identified four high-risk compounds (isolaureline, xylopine, anonaine, stepharine) and two moderate-risk compounds (coclaurine, reticuline) that may warrant clinical monitoring during concurrent chemotherapy. Conversely, acetogenins showed low oral bioavailability and minimal CYP interaction potential, suggesting limited systemic exposure. These findings suggest that specific alkaloid classes in soursop preparations may pose a greater pharmacokinetic interaction risk than previously recognized, particularly for drugs metabolized by CYP2D6. Further experimental validation is warranted to ensure the safe use of A. muricata preparations in oncology care. • Dual in silico approach assessed CYP450 interaction risk of A. muricata compounds • Aporphine alkaloids showed highest predicted CYP2D6 probabilities (85–95%) • SuperCYPsPred and SwissADME independently confirmed CYP2D6 as primary target • Acetogenins showed low oral bioavailability, mitigating herb–drug interaction risk • Four HIGH-risk compounds identified for CYP2D6-metabolized cancer therapies

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Ballesteros-Ramírez et al. (Wed,) studied this question.

synapsesocial.com/papers/69e7138bcb99343efc98d0a7 https://doi.org/https://doi.org/10.1016/j.toxrep.2026.102258

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