Authors:

L. Pangestu, W. Oktavelia, F. Ardiansyah, A. Khalilah, E. Novianti, S. Hidayat, T. N. Apriliya, Muchtaridi .

Abstract:

“Sebesar 11,7% dari 19,3 juta kasus kanker yang terjadi pada tahun 2020 merupakan kasus kanker payudara. Kanker ini umumnya disebabkan karena ekspresi berlebih dari protein HER-2 yang berperan dalam proliferasi dan pertumbuhan sel. Salah satu tipe kanker payudara, Triple Negative Breast Cancer (TNBC), menyumbang 10-20% dari semua kasus kanker payudara. Sebagai obat kanker payudara, lapatinib, telah digunakan untuk pasien kanker payudara positif-HER2. Namun, telah diketahui bahwa obat tersebut dapat meningkatkan metastasis sel TNBC. Maka, diperlukan pencarian senyawa baru yang dapat lebih efektif dan aman untuk pengobatan kanker payudara, seperti senyawa yang terkandung dalam extra virgin olive oil (EVOO) dari tanaman zaitun yang mampu menginhibisi aktivitas tirosin kinase dari protein HER-2. Tujuan dari penelitian ini adalah mengetahui interaksi molekuler dan profil farmakokinetik senyawa turunan fenolat dari kandungan EVOO. Metode yang digunakan dalam penelitian ini menggungakan metode Studi In silico dilakukan dengan simulasi penambatan molekuler, memprediksi profil farmakokinetik dan toksisitas senyawa, serta drug-likeness yang mengacu pada Lipinski’s Rule of Five. Senyawa 1-Acetoxypinoresinol merupakan senyawa terbaik berdasarkan hasil penambatan molekuler dan profil farmakokinetiknya dengan free binding energy sebesar -4,74 kcal/mol, konstanta inhibisi 335,19 µm, dan terdapat interaksi dengan residu asam amino Asn237. Adapun Nilai HIA dan caco-2 sebesar 93,96% dan 27,75%, nilai PPB dan BBB sebesar 77,58% dan 0,026%, serta tidak bersifat mutagenik dan karsinogenik. Hasil yang didapatkan menyatakan bahwa Senyawa 1-Acetoxypinoresinol memiliki potensi sebagai inhibitor HER2 yang paling baik diantara senyawa lainnya yang terdapat dalam kandungan EVOO. Kata kunci: Extra virgin olive oil, HER-2, in silico, Kanker Payudara ABSTRACT About 11.7% of the 19.3 million cancer cases in 2020 were breast cancer. This cancer is generally caused by overexpression of the HER-2 protein that plays a role in cell proliferation and growth. One type of breast cancer, Triple Negative Breast Cancer (TNBC), accounts for 10-20% of all breast cancer cases. Lapatinib is one of a drug that has been used for HER2-positive breast cancer patients. However, it’s known that the drug can promote TNBC cell metastasis. Thus, it is necessary to search for more effective and safer compounds, such as compounds contained in extra virgin olive oil (EVOO) from olive plants for breast cancer treatment that can inhibit the activity of tyrosine kinase from the HER-2 protein. The purpose was to determine molecular interactions and pharmacokinetic profiles of phenolic derivatives from EVOO. The method used in this study was In silico study method carried out by simulating molecular docking, predicting the pharmacokinetic and toxicity profiles of compounds, as well as drug-likeness that refers to Lipinski’s Rule of Five. Compound 1-Acetoxypinoresinol is the best compound based on molecular docking results and its pharmacokinetic profile with a free binding energy of -4.74 kcal/mol, an inhibition constant of 335.19 µm, and interactions with the amino acid residue Asn237. The HIA and caco-2 values ??were 93.96% and 27.75%, PPB and BBB values ??were 77.58% and 0.026%, and not mutagenic and carcinogenic. The results obtained stated that Compound 1-Acetoxypinoresinol has the potential to be the best HER2 inhibitor among other compounds contained in EVOO content. Keywords: Breast Cancer, Extra virgin olive oil, Breast Cancer, HER-2, in silico”

Keywords

Extra virgin olive oil, HER-2, in silico, Kanker Payudara ABSTRACT About 11.7% of the 19.3 million cancer cases in 2020 were breast cancer. This cancer is generally caused by overexpression of the HER-2 protein that plays a role in cell proliferation and growth. One type of breast cancer, Triple Negative Breast Cancer (TNBC), accounts for 10-20% of all breast cancer cases. Lapatinib is one of a drug that has been used for HER2-positive breast cancer patients. However, it’s known that the drug can promote TNBC cell metastasis. Thus, it is necessary to search for more effective and safer compounds, such as compounds contained in extra virgin olive oil (EVOO) from olive plants for breast cancer treatment that can inhibit the activity of tyrosine kinase from the HER-2 protein. The purpose was to determine molecular interactions and pharmacokinetic profiles of phenolic derivatives from EVOO. The method used in this study was In silico study method carried out by simulating molecular docking, predicting the pharmacokinetic and toxicity profiles of compounds, as well as drug-likeness that refers to Lipinski’s Rule of Five. Compound 1-Acetoxypinoresinol is the best compound based on molecular docking results and its pharmacokinetic profile with a free binding energy of -4.74 kcal/mol, an inhibition constant of 335.19 µm, and interactions with the amino acid residue Asn237. The HIA and caco-2 values ??were 93.96% and 27.75%, PPB and BBB values ??were 77.58% and 0.026%, and not mutagenic and carcinogenic. The results obtained stated that Compound 1-Acetoxypinoresinol has the potential to be the best HER2 inhibitor among other compounds contained in EVOO content. Keywords: Breast Cancer, Extra virgin olive oil, Breast Cancer, HER-2, in silico

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References

  • Adriani, 2018, Prediksi Senyawa Bioaktif dari Tanaman Sanrego (Lunasia amara Blanco) sebagai Inhibitor Enzim Siklooksigenase-2 (COX-2) melalui Pendekatan Molecular Docking, Jurnal Ilmiah Pena, 1 (1): 6-11
  • American Cancer Society, 2017, Breast Cancer Treatment Guideline. American Cancer Society, Atlanta
  • Cheng J, Palva AM, de Vos WM, dan Satokari R, 2013, Contribution of the intestinal microbiota to human health: from birth to 100 years of age, Curr Top Microbiol Immunol, 358: 323-346
  • Hardjono, S., 2016, Prediksi Sifat Farmakokinetik, Toksisitas dan Aktivitas Sitotoksik Turunan N-Benzoil-N’-(4-fluorofenil)tiourea sebagai Calon Obat Antikanker melalui Pemodelan Molekul, Jurnal Ilmu Kefarmasian Indonesia, 14 (2): 246-255
  • Kumar R, Giri A, dan Nadendla, RR, 2018, INSILICO ADME PROFILING OF CDK9 INHIBITORS, Journal of Scientific Research in Pharmacy, 7 (3): 30-34
  • Liao, N., 2016, HER2-positive breast cancer, how far away from the cure? on the current situation of anti-HER2 therapy in breast cancer treatment and survival patients, Chinese Clinical Oncology, 5 (3): 41
  • Mohite P.B. and Pawar D.D. 2019. In silico Prioritization of some Tetrazole Chalcones for Anticonvulsant Activity. International Journal of PharmTech Research, 12(02):155-161
  • Moral R and Escrich E. 2022. Influence of Olive Oil and Its Components on Breast Cancer: Molecular Mechanisms. Molecules, 27(2):477
  • Nowdijeh AA, Moosavi MA, Hosseinzadeh S, Soleimani M, Sabouni F, Hosseini-Mazinani M., 2019, Anti-oxidant and Selective Anti-proliferative Effects of the Total Cornicabra Olive Polyphenols on Human Gastric MKN45 Cells. Iran J Biotechnol, 11;17(1)
  • Oganesyan V, Peng L, Bee JS, Li J, Perry SR, Comer F, et al, 2018, Structural insights into the mechanism of action of a biparatopic anti-HER2 antibody. Journal of Biological Chemistry, 293 (22): 8439–8448
  • Ramirez D and Caballero J, 2018, Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data. Molecules, 23 (1038): 1-17
  • Rastini MBO, Giantari NKM, Adnyani KD, dan Laksmiani NPL, 2019, Molecular Docking Aktivitas Antikanker dari Kuersetin terhadap Kanker Payudara secara In Silico, Journal of Chemistry, 13 (2): 180-184
  • Sun TY, Wang Q, Zhang J, Wu T, dan Zhang F, 2013, Trastuzumab-Peptide interactions: mechanism and application in structure-based ligand design, International journal of molecular sciences, 14 (8): 16836–16850
  • Syahputra G, Ambarsari L, dan Sumaryada T, 2014, Simulasi Docking Kurkumin Enol Bisdemetoksikurkumin dan Analoginya sebagai Inhibitor Enzim 12-Lipoksigenase, Jurnal Biofisika, 10 (1): 55-67
  • The Global Cancer Observatory, Breast, 2020, https://gco.iarc.fr/today/data/factsheets/cancers/20-Breast-fact-sheet.pdf, 15 Maret 2021.
  • WHO, 2021, Cancer, https://www.who.int/news-room/fact-sheets/detail/cancer, 15 Maret 2021.
  • WHO, 2020, Cancer Country Profile: Indonesia https://www.who.int/cancer/country-profiles/IDN_2020.pdf?ua=1, 15 Maret 2021
  • Yazdanian M, Glynn SL, Wright JL, and Hawi A, 1998, Correlating partitioning and caco-2 cell permeability of structurally diverse small molecular weight compounds, Pharm. Res, 15: 1490–1494
  • You X, Qin Z, Yan Q, Yang S, Li Y, dan Jiang Z, 2018, Structural insights into the catalytic mechanism of a novel glycoside hydrolase family 113 -1,4-mannanase from Amphibacillus xylanus, Journal of Biological Chemistry, 293(30): 11746-11757.

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https://jurnal.harianregional.com/jchem/full-89568

Published

2023-01-31

How To Cite

PANGESTU, L. et al. STUDI IN SILICO SENYAWA FENOLIK DARI TANAMAN ZAITUN (Olea europaea L.) SEBAGAI INHIBITOR HER2 PADA KANKER PAYUDARA.Jurnal Kimia (Journal of Chemistry), [S.l.], p. 57-65, jan. 2023. ISSN 2599-2740. Available at: https://jurnal.harianregional.com/jchem/id-89568. Date accessed: 28 Aug. 2025. doi:https://doi.org/10.24843/JCHEM.2023.v17.i01.p08.

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Issue

Vol. 17, No.1, Januari 2023

Section

Articles

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