The Virtual Screening of Flavonoid Derivatives on Progesterone, Estrogen, and HER-2 Receptor for Breast Cancer Treatment Candidate
Abstract
Cancer is defined as a disease caused by progressive and abnormal cell proliferation in the body. This condition is caused by deoxyribonucleic acid (DNA) changes, which causes cells to lose their normal function. The aim of this study is to find that flavonoid compounds have a more stable interaction than tamoxifen as anti-cancer candidates. Research has been conducted in silico with molecular docking (AutodockTools-1.5.7) and molecular dynamics of 200 flavonoid compounds. Furthermore, pharmacokinetic parameters, toxicity, and the application of the Lipinski Rule of Five were investigated. Based on molecular docking results, the compounds eriocotrin, glabrol, kaempferitrin, linarin, and narirutin have more stable interactions with lower binding energy (∆G) than tamoxifen. From the results of molecular docking, molecular dynamics, and pharmacokinetic studies, it is predicted that the kaempferitrin compound can be used as an anti-cancer candidate and does not cause toxicity through further research.
Keywords
References
Alnajjar, R., Mostafa, A., Kandeil, A., Al-Karmalawy, A. A. (2020). Molecular docking, molecular dynamics, and in vitro studies reveal the potential of angiotensin II receptor blockers to inhibit the COVID-19 main protease. Heliyon, 6(12), e05641. https://doi.org/10.1016/j.heliyon.2020.e05641
Aziz, F. K., Nukitasari, C., Oktavianingrum, F. A., Aryati, L. W., Santoso, B. (2016). Hasil In Silico Senyawa Z12501572, Z00321025, SCB5631028 dan SCB13970547 dibandingkan Turunan Zerumbon terhadap Human Liver Glycogen Phosphorylase (1l5Q) sebagai Antidiabetes. Jurnal Kimia VALENSI, 2(2), 120–124. https://doi.org/10.15408/jkv.v2i2.4170
Baksi, R., Singh, D. P., Borse, S. P., Rana, R., Sharma, V., Nivsarkar, M. (2018). In vitro and in vivo anticancer efficacy potential of Quercetin loaded polymeric nanoparticles. Biomedicine and Pharmacotherapy, 106(July), 1513–1526. https://doi.org/10.1016/j.biopha.2018.07.106
Binotto, M., Reinert, T., Werutsky, G., Zaffaroni, F., Schwartsmann, G. (2020). Health-related quality of life before and during chemotherapy in patients with early-stage breast cancer. Ecancermedicalscience, 14, 1–11. https://doi.org/10.3332/ECANCER.2020.1007
Chen, X., Li, H., Tian, L., Li, Q., Luo, J., Zhang, Y. (2020). Analysis of the Physicochemical Properties of Acaricides Based on Lipinski’s Rule of Five. Journal of Computational Biology, 27(9), 1397–1406. https://doi.org/10.1089/cmb.2019.0323
Chow, E., Rendleman, C. A., Bowers, K. J., Dror, R. O., H, D., Gullingsrud, J., Sacerdoti, F. D., Shaw, D. E. (2008). Desmond Performance on a Cluster of Multicore Processors. Simulation, July, 1–14.
Dermawan, D., Sumirtanurdin, R., Dewantisari, D. (2019). Molecular Dynamics Simulation Estrogen Receptor Alpha againts Andrographolide as Anti Breast Cancer. Indonesian Journal of Pharmaceutical Science and Technology, 6(2), 65. https://doi.org/10.24198/ijpst.v6i2.18168
Villa, F. X. D, Durán-Iturbide, N. A., Ávila-Zárraga, J. G. (2021). Synthesis, molecular docking, and in silico ADME/Tox profiling studies of new 1-aryl-5-(3-azidopropyl)indol-4-ones: Potential inhibitors of SARS CoV-2 main protease. Bioorganic Chemistry, 106(October). https://doi.org/10.1016/j.bioorg.2020.104497
Eberhardt, J., Santos-Martins, D., Tillack, A. F., Forli, S. (2021). AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings. Journal of Chemical Information and Modeling, 61(8), 3891–3898. https://doi.org/10.1021/acs.jcim.1c00203
Elengoe, A., Kumar, Selvam, S., Selvarajah, M., Manikam, H., Vijaya, R. (2022). Sequence analysis and structure prediction of malaysia sars-cov-2 strain’s structural and accessory proteins. In Biointerface Research in Applied Chemistry, 12(3). https://doi.org/10.33263/BRIAC123.32593304
Ezzati, M., Yousefi, B., Velaei, K., Safa, A. (2020). A review on anti-cancer properties of Quercetin in breast cancer. Life Sciences, 248(September 2019). https://doi.org/10.1016/j.lfs.2020.117463
Ferrari, I. V., Mario, M. D. (2022). Comparison and Prediction of toxicity parameters of principal Aflatoxins , antimicrobial compounds and Antifungal Drugs by pKCSM server. International Journal of Scientific Research in Biological Sciences, 9(1), 48–52.
Frimayanti, N., Djohari, M., Khusnah, A. N. (2021). Molekular Docking Senyawa Analog Kalkon sebagai Inhibitor untuk Sel Kanker Paru-Paru A549. Jurnal Ilmu Kefarmasian Indonesia, 19(1), 87. https://doi.org/10.35814/jifi.v19i1.765
Globocan. (2020). Cancer Incident in Indonesia. International Agency for Research on Cancer, 858, 1–2. https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf
Gyebi, G. A., Ogunro, O. B., Adegunloye, A. P., Ogunyemi, O. M., Afolabi, S. O. (2021). Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CLpro): an in silico screening of alkaloids and terpenoids from African medicinal plants. Journal of Biomolecular Structure and Dynamics, 39(9), 3396–3408. https://doi.org/10.1080/07391102.2020.1764868
Halder, S. K., Ahmad, I., Shathi, J. F., Mim, M. M., Hassan, M. R., Jewel, M. J. I., Dey, P., Islam, M. S., Patel, H., Morshed, M. R., Shakil, M. S., Hossen, M. S. (2022). A Comprehensive Study to Unleash the Putative Inhibitors of Serotype2 of Dengue Virus: Insights from an In Silico Structure-Based Drug Discovery. Molecular Biotechnology, 0123456789. https://doi.org/10.1007/s12033-022-00582-1
Hanif, A. U., Lukis, P. A., Fadlan, A. (2021). Pengaruh Minimisasi Energi MMFF94 dengan MarvinSketch dan Open Babel PyRx pada Penambatan Molekular Turunan Oksindola Tersubstitusi. ALCHEMY : JOURNAL OF CHEMISTRY.
Hartini, S., Winarsih, B. D., Galih, E., Nugroho, Z., Studi, P., Ners, P. (2020). Peningkatan Pengetahuan Perawat Untuk Perawatan Anak Penderita Kanker. 3(2), 141–149.
Ivanović, V., Rančić, M., Arsić, B., Pavlović, A. (2020). Lipinski’s rule of five, famous extensions and famous exceptions. Popular Scientific Article, 3(1), 171–177.
Kikuchi, H., Yuan, B., Hu, X., Okazaki, M. (2019). Chemopreventive and anticancer activity of flavonoids and its possibility for clinical use by combining with conventional chemotherapeutic agents. American Journal of Cancer Research, 9(8), 1517–1535. http://www.ncbi.nlm.nih.gov/pubmed/31497340%0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6726994
Kumar, S., Sharma, P. P., Shankar, U., Kumar, D., Joshi, S. K., Pena, L., Durvasula, R., Kumar, A., Kempaiah, P., Poonam, Rathi, B. (2020). Discovery of New Hydroxyethylamine Analogs against 3CLproProtein Target of SARS-CoV-2: Molecular Docking, Molecular Dynamics Simulation, and Structure-Activity Relationship Studies. Journal of Chemical Information and Modeling, 60(12), 5754–5770. https://doi.org/10.1021/acs.jcim.0c00326
Leung, S. H., Bodkin, M. J., von Delft, F., Brennan, P. E., Morris, G. M. (2019). SuCOS is better than RMSD for evaluating fragment elaboration and docking poses. ChemRxiv, 1–47.
Lipinski, C. A. (2004). Lead- and drug-like compounds: The rule-of-five revolution. Drug Discovery Today: Technologies, 1(4), 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007
Mardianingrum, R., Ruswanto, R., Agustien, G. S., Nuraisah, A. (2020). The Active Compound of Bangle Essential Oil as Cyclooxygenase-2 (Cox-2) Inhibitor: In Silico Approach. Jurnal Kimia Valensi, 6(2), 156–168. https://doi.org/10.15408/jkv.v6i2.16943
Miller, K. D., Nogueira, L., Mariotto, A. B., Rowland, J. H., Yabroff, K. R., Alfano, C. M., Jemal, A., Kramer, J. L., Siegel, R. L. (2019). Cancer treatment and survivorship statistics, 2019. CA: A Cancer Journal for Clinicians, 69(5), 363–385. https://doi.org/10.3322/caac.21565
Mvondo, J. G. M., Matondo, A., Mawete, D. T., Bambi, S.-M. N., Mbala, B. M., Lohohola, P. O. (2021). In Silico ADME/T Properties of Quinine Derivatives using SwissADME and pkCSM Webservers. International Journal of TROPICAL DISEASE & Health, 42(11), 1–12. https://doi.org/10.9734/ijtdh/2021/v42i1130492
Pires, D. E. V., Blundell, T. L., Ascher, D. B. (2015). pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures. Journal of Medicinal Chemistry, 58(9), 4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104
Pratama, P. R., Isman, F., Fadlan, A. (2022). Penyelidikan Aktivitas Antikanker Payudara Oleh Minyak Atsiri Bunga Michelia Alba Secara in Silico. Jurnal Ilmu Kimia Dan Terapan, 9(1).
Protein Data Bank. (n.d.). Enabling Breakthroughs in Scientific and Biomedical Research and Education. https://www.rcsb.org/
Puspita, P. J., Ambarsari, L., Adiva, A., Sumaryada, T. I. (2021). In Silico Analysis of Glucose Oxidase H516r and H516d Mutations for an Enzymatic Fuel Cell. Jurnal Kimia Valensi, 7(2), 83–93. https://doi.org/10.15408/jkv.v7i2.20733
Putra, P. P., Fauzana, A., Lucida, H. (2020). Analisis Sifat Fisika-Kimia, Potensi Target dan Toksikologi Senyawa Isolat Murni dari Bahan Alam dengan Metode In Silico. Indonesian Journal of Pharmaceutical Science and Technology Journal Homepage, 7(3), 107–117. http://jurnal.unpad.ac.id/ijpst/UNPAD
Qasaymeh, R. M., Rotondo, D., Oosthuizen, C. B., Lall, N., Seidel, V. (2019). Predictive binding affinity of plant‐derived natural products towards the protein kinase g enzyme of mycobacterium tuberculosis (Mtpkng). Plants, 8(11), 1–14. https://doi.org/10.3390/plants8110477
Rachmania, R. A., Hariyanti, H., Zikriah, R., Sultan, A. (2018). Studi In Silico Senyawa Alkaloid Herba Bakung Putih (Crinum Asiaticum L.) pada Penghambatan Enzim Siklooksigenase (COX). Jurnal Kimia VALENSI, 4(2), 124–136. https://doi.org/10.15408/jkv.v4i2.7686
Ramadhan, D. S. F., Fakih, T. M., Arfan, A. (2020). Activity Prediction of Bioactive Compounds Contained in Etlingera elatior Against the SARS-CoV-2 Main Protease: An In Silico Approach. Borneo Journal of Pharmacy, 3(4), 235–242. https://doi.org/10.33084/bjop.v3i4.1634
Rathod, S., Shinde, K., Porlekar, J., Choudhari, P., Dhavale, R., Mahuli, D., Tamboli, Y., Bhatia, M., Haval, K. P., Al-Sehemi, A. G., Pannipara, M. (2022). Computational Exploration of Anti-cancer Potential of Flavonoids against Cyclin-Dependent Kinase 8: An In Silico Molecular Docking and Dynamic Approach. ACS Omega. https://doi.org/10.1021/acsomega.2c04837
Ruswanto, Mardianingrum, R., Siswandono, Kesuma, D. (2020). Reverse Docking, Molecular Docking, Absorption, Distribution, and Toxicity Prediction of Artemisinin as an Anti-diabetic Candidate. 15(2), 88–96.
Ruswanto, Nofianti, T., Mardianingrum, R., Lestari, T., sepriliani, a. (2018). desain dan studi in silico senyawa turunan Kuwanon-H sebagai kandidat obat Anti-HIV. Jurnal Kimia VALENSI, 4(1), 57–66. https://doi.org/10.15408/jkv.v4i1.6867
Ruswanto, R. (2015). Molecular Docking Empat Turunan Isonicotinohydrazide Pada Mycobacterium Tuberculosis Enoyl-Acyl Carrier Protein Reductase (InhA). Jurnal Kesehatan Bakti Tunas Husada: Jurnal Ilmu-Ilmu Keperawatan, Analis Kesehatan Dan Farmasi, 13(1), 135–141. https://doi.org/10.36465/jkbth.v13i1.25
Ruswanto, R., Garna, I. M., Tuslinah, L., Mardianingrum, R., Lestari, T., Nofianti, T. (2018). Kuersetin, Penghambat Uridin 5-Monofosfat Sintase Sebagai Kandidat Anti-kanker. ALCHEMY Jurnal Penelitian Kimia, 14(2), 236. https://doi.org/10.20961/alchemy.14.2.14396.236-254
Ruswanto, R., Mardianingrum, R., Yanuar, A. (2022). Computational studies of thiourea derivatives as anticancer candidates through inhibition of Sirtuin-1 (SIRT1). Jurnal Kimia Sains Dan Aplikasi, 25(3), 87–96. https://doi.org/10.14710/jksa.25.3.87-96
Ruswanto, R., Nofianti, T., Mardianingrum, R., Kesuma, D., Siswandono. (2022). Design, molecular docking, and molecular dynamics of thiourea-iron (III) metal complexes as NUDT5 inhibitors for breast cancer treatment. Heliyon, 8(9). https://doi.org/10.1016/j.heliyon.2022.e10694
Salman, M. M., Al-Obaidi, Z., Kitchen, P., Loreto, A., Bill, R. M., wade-martins, r. (2021). advances in applying computer-aided drug design for neurodegenerative diseases mootaz. International Journal of Molecular Sciences Review, 42(18), 3436–3446. https://doi.org/10.1021/jm990129n
Sari, I. W., Junaidin, Pratiwi, D. (2020). Molecular Docking Study Flavonoid Compounds From Kumis Kucing (Orthosiphon stamineus B.) In a-Glukosidase Receptor as Antidiabetic Type 2. VII(2), 54–60.
Selvakumar, P., Badgeley, A., Murphy, P., Anwar, H., Sharma, U., Lawrence, K., Lakshmikuttyamma, A. (2020). Flavonoids and other polyphenols act as epigenetic. Nutrients, 12, 1–18. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.30614
Sharma, V. R., Panwar, A., Sharma, A. K. (2020). Molecular dynamic simulation study on chromones and flavonoids for the in silico designing of a potential ligand inhibiting mTOR pathway in breast cancer. Current Pharmacology Reports, 6(6), 373–379. https://doi.org/10.1007/s40495-020-00246-1
Surabhi, S., Singh, B. (2018). Computer aided drug design: an overview. Journal of Drug Delivery and Therapeutics, 8(5), 504–509. https://doi.org/10.22270/jddt.v8i5.1894
Utami, W., Aziz, H. A., Fitriani, I. N., Zikri, A. T., Mayasri, A., Nasrudin, D. (2020). In silico anti-inflammatory activity evaluation of some bioactive compound from ficus religiosa through molecular docking approach. Journal of Physics: Conference Series, 1563(1). https://doi.org/10.1088/1742-6596/1563/1/012024
Victory, A., Syahdi, R. R., & Yanuar, A. (2018). Virtual screening of Indonesian herbal database as murine double minute-2 (MDM2) inhibitor. Pharmacognosy Journal, 10(6), 1184–1189. https://doi.org/10.5530/pj.2018.6.203
Weni, M., Safithri, M., & Seno, D. S. H. (2020). Molecular docking of active compounds Piper crocatum on the α-glucosidase enzyme as antidiabetic. Indonesian Journal of Pharmaceutical Science and Technology, 7(2), 64. https://doi.org/10.24198/ijpst.v7i2.21120
Yeni, Y., Rachmania, R. A. (2022). The prediction of pharmacokinetic properties of compounds in Hemigraphis alternata (Burm.F.) T. ander leaves using pkCSM. Indonesian Journal of Chemistry, 22(4), 1081–1089. https://doi.org/10.22146/ijc.73117
DOI: 10.15408/jkv.v9i1.31482
Refbacks
- There are currently no refbacks.
Copyright (c) 2023 Ruswanto Ruswanto, Gatut Ari Wardani, Richa Mardianingrum, Ade Dwi Septian
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
