IN SILICO MOLECULAR DOCKING, ADMET AND MOLECULAR DYNAMICS STUDIES ON AN EFFICIENT MONOMER FOR ANTI BREAST CANCER ACTIVITY

Human Epidermal Receptor-2 (HER-2) overexpression is implicated in breast cancer progression; thus, HER-2 is widely used as the target of anticancer therapy. Lapatinib is a drug widely used to inhibit the HER-2 receptor and tyrosine kinase; however, it develops drug resistance. Lutein is promising to be developed as breast cancer therapy. This study aims to determine the mechanism of inhibition of HER-2 receptor overexpression by lutein in silico. Molecular docking was carried out by optimizing the lutein and lapatinib, preparing of protein target HER-2 (PDB ID 3PP0), validating of molecular docking protocol, and docking of lutein and lapatinib on HER-2. The study resulted in the binding energy of -12.37 kcal/mol, while the binding energy of the native ligand and lapatinib to HER-2 was -10.43 kcal/mol and -12.25 kcal/mol, respectively. The binding energy showed that lutein has potential as breast anticancer suggested from the stronger affinity to HER2.

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The potency of alpha-humulene as HER-2 inhibitor by molecular docking

Pharmacy Reports ◽

10.51511/pr.19 ◽

2022 ◽

Vol 2 (1) ◽

pp. 19

Author(s):

I Made Harimbawa Putra ◽

I Putu Ari Anggara Catur Pratama ◽

Komang Dian Aditya Putra ◽

G. A. Desya Pradnyaswari ◽

Ni Putu Linda Laksmiani

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Binding Energy ◽

In Silico ◽

Van Der Waals ◽

Electrostatic Energy ◽

Protein Preparation ◽

Her 2 ◽

In Silico Molecular Docking

HER-2 overexpression is present in approximately 20% of breast cancer. This research aims to study the interactions of α-humulene to HER-2 protein by using in silico molecular docking. The experiment was carried out by HER-2 protein preparation (PDB ID 3PP0), docking validation, α-humulene optimization, and α-humulene docking. The results showed that α-humulene had binding energy of -7.50 kcal/mol, Van der Waals binding energy of -7.48 kcal/mol, and electrostatic energy of -0.02 kcal/mol. α-Humulene is potential as anti-breast cancer towards HER-2 in silico.

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

ALCHEMY Jurnal Penelitian Kimia ◽

10.20961/alchemy.17.1.43979.83-95 ◽

2021 ◽

Vol 17 (1) ◽

pp. 83

Author(s):

Richa Mardianingrum ◽

Kamiel Roesman Bachtiar ◽

Susanti Susanti ◽

Aas Nuraisah Aas Nuraisah ◽

Ruswanto Ruswanto

Keyword(s):

Breast Cancer ◽

Molecular Dynamics ◽

Molecular Docking ◽

In Silico ◽

The Body ◽

Dynamics Simulation ◽

Lipinski’S Rule ◽

Lipinski’S Rule Of Five ◽

Anti Inflammatory ◽

Cox 1

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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In silico molecular docking studies and MM/GBSA analysis of coumarin-carbonodithioate hybrid derivatives divulge the anticancer potential against breast cancer

Beni-Suef University Journal of Basic and Applied Sciences ◽

10.1186/s43088-020-00059-7 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Shridhar Veeresh Pattar ◽

Shakeel Ahamed Adhoni ◽

Chandrappa Mukappa Kamanavalli ◽

Suresh Sadashiv Kumbar

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Molecular Docking Studies ◽

In Silico Molecular Docking

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In Silico Molecular Docking Studies on the Chemical Constituents of Clerodendrum phlomidis for its Cytotoxic Potential against Breast Cancer Markers

Research Journal of Pharmacy and Technology ◽

10.5958/0974-360x.2018.00300.1 ◽

2018 ◽

Vol 11 (4) ◽

pp. 1612

Author(s):

N. Habeela Jainab ◽

M. K. Mohan Maruga Raja

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

In Silico ◽

Chemical Constituents ◽

Docking Studies ◽

Cytotoxic Potential ◽

Cancer Markers ◽

Molecular Docking Studies ◽

Clerodendrum Phlomidis ◽

In Silico Molecular Docking

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In silico molecular docking and molecular dynamics examination of Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone inhibition activity to SARS-CoV-2 main protease

BIO Web of Conferences ◽

10.1051/bioconf/20214107002 ◽

2021 ◽

Vol 41 ◽

pp. 07002

Author(s):

Raihan Kenji Rizqillah ◽

Jaka Fajar Fatriansyah ◽

Fadilah ◽

Sulhadi ◽

Siti Wahyuni ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

In Silico ◽

Andrographis Paniculata ◽

Dynamics Simulation ◽

Ligand Docking ◽

Inhibition Activity ◽

Docking Score ◽

Main Protease ◽

In Silico Molecular Docking

In this work, Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone inhibition activity to SARS CoV-2 main protease were examined through in silico molecular docking and molecular dynamics simulation, with Remdesivir as control ligand. Docking score and MMGBSA were examined as well as molecular dynamics parameters: RMSD, RMSF and Protein ligand contact fraction. Our study found that Andrographis paniculata compounds of Andrographolide, Neoandrographolide, and 5-hydroxy-7,8,2’,3’-tetramethoxyflavone have comparable inhibition activity to SARS CoV-2 main protease in comparison to Remdesivir. 5-hydroxy7,8,2’,3’-tetramethoxyflavone has the lowest docking score, which was further validated by protein ligand contact fraction examination, although MMGBSA score is lowest for Remdesivir.

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