Uji Aktivitas Senyawa Panduratin A dan Turunannya terhadap Reseptor Estrogen Alfa pada Kanker Payudara Secara In Silico
Abstract
ABSTRACT: Breast cancer is the leading cause of death in women caused by cancer. Panduratin compound derived from Boesenbergia pandurate is a compound that has anticancer activity on MCF-7 breast cancer and HT-29 colon cancer cells. The purpose of this study was to determine the interaction and affinity between the panduratin compound to alpha estrogen receptor. In this study, identification of the physicochemical properties of the Panduratin tes compound was carried out using ChemBioDraw. The Panduratin compound was geometrically optimized using Gauss View software version 5.0.8 and Gaussian version 09. The conformation of the best Panduratin compound were continued to docking simulation stage for the Alpha Estrogen Receptor which had been separated from its natural ligand and was validated using MGL Tools 1.5.6 software which has been equipped with Autodock Tools version 4.2. Analysis of the molecular docking result was conducted using BIOVIA Discovery Studio software. Toxicity prediction were performed using Toxtree software by looking at the Cramer Rules, The TCC Decision Tree and Benigni/Bossa Rulebase parameters. The result showed that Panduratin F compounds have a better affinity than Panduratin A, Panduratin B1, Panduratin C, Panduratin D, Panduratin E, Panduratin G and Panduratin H compunds and their natural ligan (4-hydroxytamoxifen) with a free energy of binding value -12,72 Kcal/mol and inhibiton constant 436,45 pM. So, Panduratin F compound can be used as a breast anticancer candidate.
Keywords: Breast cancer, estrogen receptor alpha, panduratin, in silico.
ABSTRAK: Kanker payudara merupakan penyebab kematian utama pada wanita yang disebabkan oleh kanker. Senyawa Panduratin berasal dari Boesenbergia pandurate, merupakan senyawa yang memiliki aktivitas antikanker pada sel kanker payudara MCF-7 dan kanker kolon HT-29. Tujuan dari penelitian ini untuk mengetahui interaksi dan afinitas antara senyawa panduratin dengan reseptor estrogen alfa. Pada penelitian ini dilakukan identifikasi sifat fisikokimia pada senyawa uji Panduratin menggunakan ChemBioDraw. Senyawa uji Panduratin dilakukan optimasi geometri menggunakan software Gauss View versi 5.0.8 dan Gaussian versi 09. Konformasi senyawa uji Panduratin terbaik dilanjutkan ke tahap simulasi docking terhadap reseptor estrogen alfa yang telah dipisahkan dengan ligan alaminya dan telah di validasi menggunakan software MGL Tools 1.5.6 yang telah dilengkapi dengan Autodock Tools versi 4.2. dan dilakukan analisis hasil docking menggunakan software BIOVIA Discovery Studio, senyawa dilakukan prediksi toksisitas menggunakan software Toxtree dengan melihat parameter Cramer rules, kroes TCC decision tree dan benigni/bossa rulebase. Dari hasil molecular docking dapat disimpulkan bahwa senyawa Panduratin F memiliki afinitas yang lebih baik dibandingkan senyawa Panduratin A, Panduratin B, Panduratin C, Panduratin D, Panduratin E, Panduratin G, Panduratin H dan ligan alaminya (hydroxytamoxifen) dengan nilai energi bebas ikatan -12,72 Kcal/mol dan konstanta inhibisi 436,45 pM sehingga dapat dijadikan sebagai referensi obat antikanker payudara.
Kata Kunci: Kanker payudara, reseptor estrogen alfa, panduratin, in silico.
Keywords
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DOI: http://dx.doi.org/10.29313/.v0i0.29610
