Electronic Theses and Dissertation

Kanker kolorektal merupakan salah satu penyebab utama kematian akibat kanker secara global, dengan kemoterapi standar seperti 5-fluorouracil (5-fu) sering mengalami penurunan efektivitas akibat resistensi sel kanker. tanaman pala (myristica fragrans) memiliki berbagai aktivitas farmakologis yang berpotensi menjadi sumber agen antikanker baru melalui mekanisme multitarget. penelitian ini bertujuan untuk mengidentifikasi senyawa bioaktif dari tanaman pala, memprediksi mekanisme molekulernya, serta mengevaluasi potensinya sebagai kandidat antikanker kolorektal menggunakan pendekatan in silico. profil senyawa kimia minyak atsiri pala dianalisis menggunakan gas chromatography-mass spectrometry (gc-ms), dilengkapi dengan data senyawa dari basis data knapsack. analisis network pharmacology dilakukan untuk mengidentifikasi target protein potensial dan jalur pensinyalan, yang kemudian divalidasi melalui molecular docking untuk menilai afinitas ikatan antara senyawa aktif dan protein target utama. analisis ini melibatkan 75 senyawa yang diperoleh dari hasil gc–ms dan basis data knapsack. studi network pharmacology mengidentifikasi 11 protein hub utama, termasuk akt1, mapk1, src, tp53, dan esr1 yang berperan penting dalam regulasi jalur pensinyalan pi3k-akt dan mapk. hasil molecular docking menunjukkan bahwa senyawa golongan lignan, khususnya nectandrin b, memiliki potensi inhibisi terbaik dengan afinitas pengikatan terkuat terhadap protein akt1 (-9,6 kkal/mol). afinitas ini terbukti lebih kuat dibandingkan dengan obat standar 5-fluorouracil pada berbagai target protein yang diuji. senyawa nectandrin b dari tanaman pala berpotensi dikembangkan sebagai agen antikanker kolorektal multitarget yang efektif melalui modulasi jalur proliferasi dan apoptosis sel kanker. kata kunci: myristica fragrans, kanker kolorektal, network pharmacology, molecular docking

Colorectal cancer is one of the leading causes of cancer-related mortality worldwide, and standard chemotherapy such as 5-Fluorouracil (5-FU) often shows reduced effectiveness due to the development of cancer cell resistance. Nutmeg (Myristica fragrans) possesses various pharmacological activities and has potential as a source of novel anticancer agents through multitarget mechanisms. This study aimed to identify bioactive compounds from nutmeg, predict their molecular mechanisms, and evaluate their potential as colorectal anticancer candidates using an in silico approach. The chemical profile of nutmeg essential oil was analyzed using Gas Chromatography–Mass Spectrometry (GC–MS) and complemented with compound data from the KNApSAcK database. Network pharmacology analysis was performed to identify potential protein targets and signaling pathways, which were subsequently validated by molecular docking to assess the binding affinity between active compounds and key protein targets. A total of 75 compounds derived from GC–MS analysis and the KNApSAcK database were included in this analysis. Network pharmacology identified 11 major hub proteins, including AKT1, MAPK1, SRC, TP53, and ESR1, which play important roles in the regulation of the PI3K-Akt and MAPK signaling pathways. Molecular docking results showed that lignan compounds, particularly Nectandrin B, exhibited the strongest inhibitory potential with the highest binding affinity toward AKT1 (−9.6 kcal/mol). This affinity was stronger than that of the standard drug 5-Fluorouracil across the tested protein targets. Nectandrin B from nutmeg therefore shows promising potential as an effective multitarget agent for colorectal cancer through modulation of cancer cell proliferation and apoptosis pathways. Keywords: Myristica fragrans, Colorectal cancer, Network Pharmacology, Molecular Docking