Uji In-Silico Aktivitas Antikanker Paru Senyawa Vanilloid pada Jahe Merah (Zingiber officinale Roscoe.) terhadap Epidermal Growth Factor Receptor (Egfr) Exon 20
Authors: Syahrizal Nazala  , Diar Herawati  , Taufik Muhammad Fakih  
Published: September 2022

Abstract. The anticancer activity of vanilloid compounds in red ginger is thought to have an interaction with the Epidermal Growth Factor Receptor (EGFR) Exon 20 which affects the growth of lung cancer cells. The purpose of this study was to observe the interaction of vanilloid compounds with EGFR Exon 20 and to predict the activity, absorption, distribution and toxicity of vanilloid compounds. All test compounds were optimized by Gauss View software version 5.0.8 and Gaussian version 09, then molecular docking simulations were carried out as well as absorption, distribution and toxicity predictions. Of the 7 vanilloid compounds that were docked, hexahydrocurcumin showed potential as an anticancer compound. Hexahydrocurcumin is declared to meet the requirements of the Lipinski Rule of Five, which means it has good bioavailability. Prediction of absorption and distribution includes the percentage values of Human Intestinal Absorption (HIA), human colon adenocarcinoma (Caco-2), and Plasma Binding Protein (PPB). Toxicity test showed that hexahydrocurcumin compound was mutagenic but not carcinogenic. The molecular docking simulation results showed that the hexahydrocurcumin compound had a better affinity for EGFR Exon 20 compared to other vanilloid compounds. Visualization results showed that hexahydrocurcumin compounds had interactions with amino acid residues Lys129, Leu83, Thr165, Ile10, Asp145, Asp86, Gln31, Phe80, Gln85 and Ala144. The results showed that the hexahydrocurcumin compound had anti-lung cancer candidate activity to EGFR Exon 20 receptor.

Abstrak. Aktivitas antikanker senyawa vanilloid pada jahe merah diduga memiliki interaksi dengan Epidermal Growth Factor Receptor (EGFR) Exon 20 yang berperaruh terhadap pertumbuhan sel kanker paru. Tujuan penelitian ini adalah untuk melihat interaksi senyawa vanilloid terhadap EGFR Exon 20 dan mendapatkan prediksi aktivitas, absorpsi, distribusi serta toksisitas senyawa vanilloid. Semua senyawa uji dioptimasi dengan software Gauss View versi 5.0.8 dan Gaussian versi 09 kemudian dilakukan simulasi molecular docking serta prediksi absorpsi, distribusi dan toksisitasnya. Dari 7 senyawa vanilloid yang di dockingkan, hexahydrocurcumin menunjukan potensi sebagai senyawa untuk antikanker. Hexahydrocurcumin dinyatakan memenuhi aturan Lipinski’s Rule of Five yang berarti memiliki bioavailabilitas yang baik. Prediksi absorpsi dan distribusi meliputi nilai persentase Human Intestinal Absorption (HIA), human colon adenocarcinoma (Caco-2), dan Protein Plasma Binding. Pengujian toksisitas menunjukkan bahwa senyawa hexahydrocurcumin bersifat mutagenik namun tidak karsinogenik. Hasil simulasi molecular docking menunjukkan bahwa senyawa hexahydrocurcumin memiliki afinitas yang lebih baik terhadap EGFR Exon 20 dibandingkan dengan senyawa vanilloid lainnya. Hasil visualisasi menunjukkan bahwa senyawa hexahydrocurcumin memiliki interaksi dengan residu asam amino Lys129, Leu83, Thr165, Ile10, Asp145, Asp86, Gln31, Phe80, Gln85 dan Ala144. Hasil yang didapat menunjukkan bahwa senyawa hexahydrocurcumin memiliki potensi untuk dijadikan kandidat anti kanker paru terhadap reseptor EGFR Exon 20.