Studi in silico Metabolit Sekunder Brucea javanica sebagai Inhibitor EGFR Mutan T790M-L858R-V948R (In Silico Study of Secondary Metabolites from Brucea Javanica as EGFR Mutant T790M-L858R-V948R Inhibitor)

Proceedings of the National Seminar of Pharmacy SEFADROKSIL 2016

14 Pages Posted: 9 Aug 2017

Date Written: October 1, 2016

Abstract

Indonesian Abstract: Brucea javanica diketahui memiliki banyak metabolit sekunder dengan beragam aktivitas, seperti antimalaria, antimikroba, maupun antikanker. Ekstrak Brucea javanica diketahui dapat menghambat perkembangan Non-Small Cell Lung Cancer (NSCLC). Salah satu penyebab terjadinya NSCLC adalah mutasi pada Epidermal Growth Factor Receptors (EGFR), suatu reseptor epidermal yang meregulasi proses proliferasi sel. Mutasi pada EGFR terutama pada posisi T790M, L858R dan V948R adalah salah satu penyebab overproliferasi pada sel. Penelitian ini bertujuan untuk mengetahui jenis metabolit sekunder dari Brucea javanica dengan potensi paling besar sebagai inhibitor EGFR mutan T790M-L858R-V948R. Metode yang digunakan adalah molecular docking beberapa metabolit sekunder Brucea javanica terhadap EGFR mutan T790M-L858R-V948R, dengan bruceajavanin A menunjukkan energi bebas ikatan paling negatif dan konstanta inhibisi paling kecil, secara berturut-turut sebesar -9,93 kcal/mol dan 52,67 nM. Bruceajavanin A menunjukkan afinitas lebih tinggi pada EGFR mutan T790M-L858R-V948R dibandingkan EGFR wild type, dimana interaksi pada asam amino posisi 790-800 terutama pada 795-Phe memiliki pengaruh penting terhadap afinitas bruceajavanin A. Hasil tersebut memberikan prediksi bahwa bruceajavanin A memiliki aktivitas sebagai inhibitor EGFR mutan T790M-L858R-V948R dan memiliki potensi untuk dikembangkan pada terapi NSCLC.

English Abstract: Brucea javanica was known for having many secondary metabolites with various activities such as antimalarial, antimicrobial, or anticancer. Brucea javanica extract was known for inhibits the development of Non-Small Cell Lung Cancer (NSCLC). One of the causes of NSCLC is mutations in Epidermal Growth Factor Receptors (EGFR), epidermal receptors that regulate cell proliferation processes. Mutations in EGFR mainly on position T790M, L858R and V948R is one of the causes of overproliferation cell. The present study aims to determine the most potent secondary metabolites of Brucea javanica as EGFR mutan T790M-L858R-V948R inhibitor, with bruceajavanin A provide most negative free energy of binding and lowest inhibition constants -9.93 kcal/mol and 52.67 nM, respectively. Bruceajavanin A show higher affinity towards EGFR mutant T790M-L858R-V948R than EGFR wild type, with interactions at position 790-800 particularly on 795-Phe had important influences towards affinity of bruceajavanin A. This results predicted that bruceajavanin A has activity as EGFR mutant T790M-L858R-V948R inhibitor and should be potential to be developed as NSCLC therapy

Note: Downloadable document is in Indonesian.

Keywords: Brucea Javanica, Bruceajavanin A, Docking, EGFR, NSCLC

Suggested Citation

Pratama, Mohammad Rizki Fadhil, Studi in silico Metabolit Sekunder Brucea javanica sebagai Inhibitor EGFR Mutan T790M-L858R-V948R (In Silico Study of Secondary Metabolites from Brucea Javanica as EGFR Mutant T790M-L858R-V948R Inhibitor) (October 1, 2016). Proceedings of the National Seminar of Pharmacy SEFADROKSIL 2016, Available at SSRN: https://ssrn.com/abstract=3007743

Mohammad Rizki Fadhil Pratama (Contact Author)

Universitas Muhammadiyah Palangkaraya ( email )

RTA Milono Street Km. 1.5
Palangka Raya, Central Kalimantan 73111
Indonesia

HOME PAGE: http://www.umpalangkaraya.ac.id

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