In Silico Study and Pharmacokinetics Prediction of ɛ-Viniferin Compound as Anticancer Drug Candidate
Downloads
The ɛ-Viniferin (ɛ-VNF) is a resveratrol dimer found in grapes (Vitis vinifera) which is thought to have anticarcinogenic activity. Breast cancer is one of the biggest causes of mortality in women. Current conventional chemotherapy can give negative side effects for cancer patients. Therefore, exploration to find an alternative modality is required. HER2 (Human Epidermal Growth Factor Receptor 2) and CDK6 (Cyclin Dependent Kinase 6) are two proteins that play an important role in breast cancer cell proliferation and differentiation. This study aimed to determine the potential of ɛ-VNF in inhibiting HER2 and CDK6 by molecular docking study. This research was conducted in silico using AutoDockTools v1.5.7 software. The results were validated with PyMOL and visualized in Discovery Studio Visualizer software to see the amino acid residues generated. Prediction of pharmacokinetics and toxicity profiles of the compound were performed with SwissADME and ADMETLab web tools. The results showed that ɛ-VNF was able to bind to HER2 and CDK6 receptors with binding energies of -10,45 kcal/mol and -7,56 kcal/mol, respectively. In silico pharmacokinetics and toxicity studies showed that ɛ-VNF fulfills Lipinski’s Rule of Five and has the potential to be used as a drug candidate. Overall, the results of this study indicate that ɛ-VNF has the potential to be further investigated and developed as an anticancer drug candidate through inhibition of HER2 and CDK6 receptors.
Downloads
Akinwumi BC, Bordun KAM, Anderson HD. Biological activities of stilbenoids. International Journal of Molecular Sciences. 2018 Mar;19(3):792.
Fuloria S, Sekar M, Khattulanuar FS, Gan SH, Rani NNIM, Ravi S, et al. Chemistry, biosynthesis and pharmacology of viniferin: potential resveratrol-derived molecules for new drug discovery, development and therapy. Molecules. 2022 Aug;27(16):5072.
Courtois A, Jourdes M, Dupin A, Lapèze C, Renouf E, Biais B, et al. In vitro glucuronidation and sulfation of ε-viniferin, a resveratrol dimer, in humans and rats. Molecules. 2017 May;22(5):733.
Andreani C, Bartolacci C, Wijnant K, Crinelli R, Bianchi M, Magnani M, et al. Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor. Aging (Albany NY). 2017 Feb;9(2):508–20.
Kashyap D, Pal D, Sharma R, Garg VK, Goel N, Koundal D, et al. Global increase in breast cancer incidence: risk factors and preventive measures. BioMed Research International. 2022 Apr;2022. doi: 10.1155/2022/9605439.
Rinnerthaler G, Gampenrieder SP, Greil R. HER2 Directed antibody-drug-conjugates beyond T-DM1 in breast cancer. International Journal of Molecular Sciences. 2019 Jan;20(5):1115.
Daemen A, Manning G. HER2 is not a cancer subtype but rather a pan-cancer event and is highly enriched in AR-driven breast tumors. Breast Cancer Research. 2018 Jan;20(1):8.
Lynce F, Shajahan-Haq AN, Swain SM. CDK4/6 inhibitors in breast cancer therapy: current practice and future opportunities. Pharmacology & Therapeutics. 2018 Nov;191:65–73.
Al-Mahayri ZN, Patrinos GP, Ali BR. Toxicity and pharmacogenomic biomarkers in breast cancer chemotherapy. Frontiers in Pharmacology. 2020 Apr;11:445.
George BP, Chandran R, Abrahamse H. Role of phytochemicals in cancer chemoprevention: insights. Antioxidants. 2021 Sep;10(9):1455.
Torres PHM, Sodero ACR, Jofily P, Silva-Jr FP. Key topics in molecular docking for drug design. International Journal of Molecular Sciences. 2019 Sep;20(18):4574.
C S, S DK, Ragunathan V, Tiwari P, A S, P BD. Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. Journal of Biomolecular Structure and Dynamics. 2022 Feb;40(2):585–611.
El-Banna AA, Darwish RS, Ghareeb DA, Yassin AM, Abdulmalek SA, Dawood HM. Metabolic profiling of Lantana camara L. using UPLC-MS/MS and revealing its inflammation-related targets using network pharmacology-based and molecular docking analyses. Scientific Reports. 2022 Sep;12:14828.
Nedyalkova M, Vasighi M, Sappati S, Kumar A, Madurga S, Simeonov V. Inhibition ability of natural compounds on receptor-binding domain of SARS-CoV2: an in silico approach. Pharmaceuticals (Basel). 2021 Dec;14(12):1328.
Isnawati A, Adelina R. Studi docking molekuler catechin gallate, epicatechin gallate, gallocatechin gallate, dan epigallocatechin gallate. Jurnal Kefarmasian Indonesia. 2015;5(1):25-32.
Herman R. Studi in silico lima senyawa aktif sebagai penghambat protein virus dengue. Jurnal Kefarmasian Indonesia. 2019;9(1):40-7.
Lisnasari BRW, Budiatin AS, Ardianto C, Khotib J. Molecular docking of active compound of lavandula angustifolia mill essential oil against n-methyl-d-aspartate (NMDA) receptor. Jurnal Farmasi dan Ilmu Kefarmasian Indonesia. 2022 Apr;9(1):75–81.
Sun Y, Zhou QM, Lu YY, Zhang H, Chen QL, Zhao M, et al. Resveratrol inhibits the migration and metastasis of MDA-MB-231 human breast cancer by reversing TGF-β1-induced epithelial-mesenchymal transition. Molecules. 2019 Mar;24(6):1131.
Xue YQ, Di JM, Luo Y, Cheng KJ, Wei X, Shi Z. Resveratrol oligomers for the prevention and treatment of cancers. Oxidative Medicine and Cellular Longevity. 2014;2014. doi: 10.1155/2014/765832.
Guo K, Feng Y, Zheng X, Sun L, Wasan HS, Ruan S, et al. Resveratrol and its analogs: potent agents to reverse epithelial-to-mesenchymal transition in tumors. Frontiers in Oncology. 2021 Apr;11:644134.
Cocetta V, Quagliariello V, Fiorica F, Berretta M, Montopoli M. Resveratrol as chemosensitizer agent: state of art and future perspectives. International Journal of Molecular Sciences. 2021 Feb;22(4):2049.
Arienti C, Pignatta S, Tesei A. epidermal growth factor receptor family and its role in gastric cancer. Frontiers in Oncology [Internet]. 2019 [cited 2023 Jul 11];9. Available from: https://www.frontiersin.org/articles/10.3389/fonc.2019.01308
Hart V, Gautrey H, Kirby J, Tyson-Capper A. HER2 splice variants in breast cancer: investigating their impact on diagnosis and treatment outcomes. Oncotarget. 2020 Nov;11(46):4338–57.
Łukasik P, Załuski M, Gutowska I. Cyclin-dependent kinases (CDK) and their role in diseases development–review. International Journal of Molecular Sciences. 2021 Mar;22(6):2935.
Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, et al. The Roles of Cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer. International Journal of Molecular Sciences. 2020 Mar;21(6):1960.
Nebenfuehr S, Kollmann K, Sexl V. The role of CDK6 in cancer. International Journal of Cancer. 2020 Dec;147(11):2988–95.
Hu Q, Feng M, Lai L, Pei J. Prediction of drug-likeness using deep autoencoder neural networks. frontiers in genetics [Internet]. 2018 [cited 2022 Dec 29];9. Available from: https://www.frontiersin.org/articles/10.3389/fgene.2018.00585
Owoloye AJ, Ligali FC, Enejoh OA, Musa AZ, Aina O, Idowu ET, et al. Molecular docking, simulation and binding free energy analysis of small molecules as PfHT1 inhibitors. PloS One. 2022;17(8):e0268269.
Liu K, Watanabe E, Kokubo H. Exploring the stability of ligand binding modes to proteins by molecular dynamics simulations. Journal of Computer-Aided Molecular Design. 2017 Feb;31(2):201–11.
Copyright (c) 2023 Jurnal Kefarmasian Indonesia
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.