Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer

Dermawan, Doni; Sumirtanurdin, Riyadi; Dewantisari, Deti

doi:10.24198/ijpst.v6i2.18168

Cited by 14 publications

(10 citation statements)

References 11 publications

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“…Jika lingkungan di sekitar kompleks protein ligan terdapat air, maka akan terbentuk ikatan hidrogen dengan air sehingga akan sulit menganalisis interaksi ikatan hidrogen pada proteinligan. Keadaan ini akan berdampak pada hasil kalkulasi energi kinetika dari interaksi intramolekul protein ligan yang terbentuk (9). Setelah itu dilakukan penambahan atom hydrogen dengan menggunakan software Autodock Tools versi 4.2.…”

Section: Preparasi Struktur Makromolekulunclassified

Uji Aktivitas dan Toksisitas Secara In Silico Senyawa Turunan Flavonoid pada Jeruk Bali (Citrus Maxima) sebagai Antimelanogenesis

Dyanira

Fakih

Wisnuwardhani

2022

BCSP

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Abstract. Melanogenesis is the production of the pigment melanin, which is produced by cells called melanocytes. The enzyme that plays an important role in the melanin synthesis pathway is tyrosinase. Flavonoid compounds can prevent the process of melanogenesis because it contains antioxidants. Identification of flavonoids showed that grapefruit (Ctrus maxima) contains flavonoid compounds acacetin and tangeretin, rutin, eriocitrin, hespiridine, and naringenin. The purpose of this study was to test the activity of flavonoid derived compounds in grapefruit (Citrus maxima) as an antimelanogenesis candidate with tyrosinase receptors in silico. In this research, identification of physicochemical properties of flavonoid derivative test compounds using ChemBioDraw 2D software was carried out. The test compounds for flavonoid derivatives were optimized using the Gauss View software version 5.0.8 and Gaussian version 09. Then proceed to the docking simulation stage for the flavonoid derivative test compounds to the tyrosinase receptor which has been separated from its natural ligand and has been validated using the MGL Tools 1.5.6 software. has been equipped with Autodock Tools version 4.2. Based on the research results, the docking result of acacetin compound has a good affinity value compared to other compounds, namely -5.96 kcal/mol. Predicted results of acacetin toxicity have a high toxicity potential, are within the exposure threshold with a low risk of exposure and cannot cause carcinogenicity or mutagenicity. Abstrak. Melanogenesis merupakan produksi dari pigmen melanin yang diproduksi oleh sel yang disebut dengan melanosit. Enzim yang berperan penting pada jalur sintesis melanin adalah tyrosinase. Senyawa flavonoid dapat mencegah terjadinya proses melanogenesis karena terkandung antioksidan didalamnya. Identifikasi flavonoid menunjukkan dalam Jeruk bali (Citrus maxima) mengandung senyawa flavonoid acacetin dan tangeretin, rutin, eriocitrin, hespiridin, dan naringenin. Tujuan dilakukannya penelitian ini untuk menguji aktivitas senyawa turunan flavonoid pada Jeruk bali (Citrus maxima) sebagai kandidat antimelanogenesis dengan reseptor tyrosinase seacara in silico. Pada penelitian ini dilakukan identifikasi sifat fisikokimia pada senyawa uji turunan flavonoid menggunakan software ChemBioDraw 2D. Senyawa uji turunan flavonoid dilakukan optimasi menggunakan software Gauss View versi 5.0.8 dan Gaussian versi 09. Kemudian dilanjutkan ke tahap simulasi docking senyawa uji turunan flavonoid terhadap reseptor tyrosinase 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. Berdasarkan hasil penelitan, hasil docking dar senyawa acacetin memiliki nilai afinitas yang baik dibandingkan dengan senyawa yang lain yaitu -5,96kcal/mol. Hasil prediksi toksisitas acacetin memiliki potensi toksisitas yang tinggi, berada dalam ambang batas paparan dengan resiko paparan yang masih rendah serta tidak dapat menyebabkan karsinogenik atau mutagenisitas.

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Section: Preparasi Struktur Makromolekulunclassified

Uji Aktivitas dan Toksisitas Secara In Silico Senyawa Turunan Flavonoid pada Jeruk Bali (Citrus Maxima) sebagai Antimelanogenesis

Dyanira

Fakih

Wisnuwardhani

2022

BCSP

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“…The next step is determining the system's initial coordinate point and minimization in three-step with the addition of ions and solvation. Then, the system equilibration is carried out through a gradual heating of 0º to 310K, accompanied by a decrease in resistance and a constant change of resistance for 5 ns (Dermawan et al, 2019;Case et al, 2014;.…”

Section: Molecular Dynamics Simulationmentioning

confidence: 99%

Computational Study of 1-(3-Nitrobenzoyloxymethyl)-5-Fluorouracyl Derivatives as Colorectal Cancer Agents

Mardianingrum

Susilawati

Ruswanto

2022

Valensi

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Cancer is one of the chronic diseases with a reasonably high increase at this time. One type of cancer with the highest mortality rate is colorectal cancer. Colorectal cancer is cancer that occurs in the colon and rectum. Based on GLOBOCAN data (2018), cases of colorectal cancer in Indonesia reached 8.6% or 30,017 people and were the second most common cause of death in men and the third in women. The development of cancer drugs to obtain drugs with better activity, lower toxicity, and working more selectively through structural modifications is still being carried out until now. This study aims to determine the pharmacokinetic properties and stable interactions between the thymidylate synthase and one of the 78 derivatives of 1-(3-nitrobenzoiloximethyl)-5-fluorouracyl (NB5FU) by in silico, namely molecular docking, and molecular dynamics simulations. The result shows that the NB5FU78 derivative compounds have better pharmacokinetic properties than NB5FU. Lipinski's rules of five criteria that fill the requirements have a smaller free bond energy value than NB5FU. Based on the results of molecular dynamics simulations carried out for 5 ns, the NB5FU78 derivative has a stable interaction with the thymidylate synthase (TS) receptor with total bond energy of -36.36 kcal/mol.

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“…Reseptor yang digunakan pada penelitian ini diunduh dari situs Protein Data Bank (PDB) yang kemudian dipisahkan dengan ligan dan air serta ditambahkan muatan (Dermawan et al, 2019). Ligan dari hasil analisis GC-MS minyak atsiri rimpang bangle (Zingiber purpureum Roxb.)…”

Section: Metode Penelitian Preparasi Ligan Dan Proteinunclassified

Studi In Silico Senyawa 1,4-Naphthalenedione-2-Ethyl-3-Hydroxy sebagai Antiinflamasi dan Antikanker Payudara

et al. 2021

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Inflamasi merupakan suatu respon dari tubuh terhadap adanya cedera maupun infeksi yang ditandai dengan timbulnya kemerahan, demam, bengkak, nyeri dan hilangnya fungsi. Inflamasi berkontribusi terhadap ketidakseimbangan sekresi sitokin yang akan menghambat terjadinya apoptosis pada sel kanker sehingga menyebabkan hiperproliferasi sel. Kanker payudara merupakan salah satu penyakit kanker dengan prevalensi tertinggi di urutan ke dua di dunia. Penelitian terdahulu melaporkan pemberian minyak atsiri rimpang bangle (Zingiber purpureum Roxb.) secara topikal mampu memberikan penghambatan inflamasi yang lebih tinggi daripada triamcinolone, namun spesifik senyawa yang berpotensinya belum diketahui. Tujuan dari penelitian ini, yakni mencari senyawa aktif hasil analisis GCMS minyak atsiri rimpang bangle yang berpotensi sebagai antiinflamasi dan antikanker payudara secara in silico. Metode yang digunakan berupa screening Lipinski’s rule of Five, farmakokinetika dan toksisitas senyawa hasil analisis GC-MS, serta penambatan molekul dan dinamika molekular. Hasil screening dan simulasi penambatan molekul menunjukkan bahwa senyawa 1,4-naphthalenedione-2-ethyl-3-hydroxy dapat berikatan dengan reseptor COX-1 (antiinflamasi), dan hERα (antikanker payudara), namun lebih selektif terhadap reseptor COX-1 dengan nilai energi bebas (ΔG) yang lebih kecil yakni sebesar -7,20 kkal/mol, dibandingkan dengan interaksinya terhadap reseptor Erα yang bernilai -6,00 kkal/mol. Hasil simulasi dinamika molekular menggunakan metode kalkulasi MM-GBSA menunjukkan bahwa kompleks (1,4-naphthalenedione-2-ethyl-3-hydroxy)-(COX-1) memiliki nilai ∆GTOTAL sebesar -24,22 kkal/mol. Nilai ini lebih kecil dibandingkan dengan ∆GTOTAL kompleks (1,4-naphthalenedione-2-ethyl-3-hydroxy)-(hErα) sebesar -8,92 kkal/mol). Hal ini menunjukkan bahwa tingkat afinitas 1,4-naphthalenedione-2-ethyl-3-hydroxy terhadap COX-1 diprediksi lebih baik dan lebih poten sebagai antiinflamasi dibandingkan sebagai antikanker payudara.In Silico Study of 1,4-Naphthalenedione-2-Ethyl-3-Hydroxy Compounds as Anti-inflamation dan Breast Anticancer. Inflammation is a response from the body to injury or infection which is characterized by redness, fever, swelling, pain, and loss of function. Inflammation contributes to the imbalance of cytokine secretion which will inhibit apoptosis in cancer cells, causing cell hyperproliferation. Breast cancer is one of the cancer diseases with the second-highest prevalence in the world. The pioneering works reported that topical application of Bangle (Zingiber purpureum R) was able to provide a higher inhibition of inflammation than triamcinolone, however, the specific potential of the compound was unknown. The purpose of this study is to find active compounds that have the potential to be anti-inflammatory and anti-cancer in the breast using in silico approach. The methods used are screening Lipinski’s Rule of Five, pharmacokinetics and toxicity of compounds from GC-MS analysis and molecular docking, and molecular dynamics. The screening and molecular docking simulation results showed that the compound 1,4-naphthalenedione-2-ethyl-3-hydroxy can bind to COX-1 (anti-inflammatory), and ERα (Estrogen Reseptor α), but was more selective towards COX-1 receptor with a binding affinity (ΔG) -7.20 kcal/mol, compare to its interaction with ERα which is -6.00 kcal/mol. The results of molecular dynamics simulation using the MM-GBSA calculation method show that the complex (1,4-naphthalenedione-2-ethyl-3-hydroxy)-(COX-1) has a value of ∆GTOTAL of -24.22 kcal/mol). This value is smaller than ∆GTOTAL of the complex (1,4-naphthalenedione-2-ethyl-3-hydroxy)-(hErα) of -8.92 kcal/mol. The results indicate that the affinity level of 1,4-naphthalenedione-2-ethyl-3-hydroxy to COX-1 was predicted to be better and more potent as an anti-inflammatory than as an anti-breast cancer.

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Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer

Cited by 14 publications

References 11 publications

Uji Aktivitas dan Toksisitas Secara In Silico Senyawa Turunan Flavonoid pada Jeruk Bali (Citrus Maxima) sebagai Antimelanogenesis

Uji Aktivitas dan Toksisitas Secara In Silico Senyawa Turunan Flavonoid pada Jeruk Bali (Citrus Maxima) sebagai Antimelanogenesis

Computational Study of 1-(3-Nitrobenzoyloxymethyl)-5-Fluorouracyl Derivatives as Colorectal Cancer Agents

Studi In Silico Senyawa 1,4-Naphthalenedione-2-Ethyl-3-Hydroxy sebagai Antiinflamasi dan Antikanker Payudara

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