Electronic Theses and Dissertation

Voacanga foetida secara tradisional digunakan untuk pengobatan, dan senyawa voacangine-nya menunjukkan aktivitas sitotoksik. Namun, profil keamanan dan potensi toksisitasnya belum sepenuhnya diketahui. Tujuan penelitian ini memprediksi potensi toksisitas pernapasan dan interaksi molekuler voacangine terhadap target biologis secara in silico. Penelitian ini menggunakan metode pendekatan network toxicology dan molecular docking. Toksisitas akut dan LD50 diprediksi dengan ProTox-II. Target gen voacangine dan toksisitas pernapasan diidentifikasi melalui SwissTargetPrediction dan GeneCards, kemudian dianalisis irisan, enrichment (GO dan KEGG), serta interaksi protein-protein (PPI). Sepuluh target teratas dari analisis PGI kemudian divalidasi dengan docking molekuler menggunakan MOE untuk menganalisis afinitas pengikatan (ΔGbinding), interaksi ikatan hidrogen, dan status fungsional voacangine. Hasil penelitian voacangine diprediksi memiliki toksisitas oral akut (LD50 40 mg/kg BB) dengan organ target pernapasan. Teridentifikasi 81 gen target irisan yang terlibat dalam jalur kunci seperti VEGF, MAPK, dan signaling kalsium yang terkait dengan mekanisme toksisitas pernapasan. Analisis docking pada 10 target terpenting (ESR1, EGFR, PTGS2, MMP2, SIRT1, KDR, IGF1R, BCL2, ABCB1, dan SLC6A4) menunjukkan voacangine berikatan kuat pada semua target. Voacangine diprediksi sebagai aktivator pada ESR1 dan EGFR, namun berperan sebagai inhibitor pada kedelapan target lainnya (seperti PTGS2, BCL2, dan SLC6A4). Secara komputasi, voacangine menunjukkan potensi efek polifarmasi yang kompleks. Sementara aktivitas inhibisinya menjanjikan untuk efek terapeutik, prediksi sebagai aktivator ESR1/EGFR serta keterlibatannya dalam jalur biologis terkait toksisitas pernapasan mengindikasikan potensi risiko yang perlu diwaspadai.

Kata Kunci: Voacanga foetida, voacangine, toksisitas pernapasan, network toxicology, docking molekuler.

Voacanga foetida is traditionally used for medicinal purposes, and its compound voacangine demonstrates cytotoxic activity. However, its safety profile and potential toxicity are not yet fully understood. The objective of this research is to predict the potential respiratory toxicity and molecular interactions of voacangine with biological targets using in silico methods. This study employs network toxicology and molecular docking approaches. Acute toxicity and LD50 were predicted using ProTox-II. Voacangine target genes and respiratory toxicity-related genes were identified through SwissTargetPrediction and GeneCards, followed by intersection analysis, enrichment analysis (GO and KEGG), and protein-protein interaction (PPI) analysis. The top ten targets from the PPI analysis were then validated through molecular docking using MOE to analyze binding affinity (ΔGbinding), hydrogen bond interactions, and the functional status of voacangine. The results indicate that voacangine is predicted to have acute oral toxicity (LD50 40 mg/kg body weight) with the respiratory system as the target organ. Eighty-one intersecting target genes were identified, involved in key pathways such as VEGF, MAPK, and calcium signaling, which are associated with respiratory toxicity mechanisms. Docking analysis on the ten most important targets (ESR1, EGFR, PTGS2, MMP2, SIRT1, KDR, IGF1R, BCL2, ABCB1, and SLC6A4) showed that voacangine binds strongly to all targets. Voacangine is predicted to act as an activator for ESR1 and EGFR, but functions as an inhibitor for the other eight targets (such as PTGS2, BCL2, and SLC6A4). Computationally, voacangine exhibits a complex polypharmacological effect potential. While its inhibitory activity is promising for therapeutic effects, its predicted role as an activator of ESR1/EGFR, along with its involvement in biological pathways related to respiratory toxicity, indicates potential risks that need to be monitored. Keywords: Voacanga foetida, voacangine, respiratory toxicity, network toxicology, molecular docking.