Asita Elengoe
ABSTRACT
The leading cause of cancer-related deaths among women is breast cancer. Breast cancer indicators can be blocked by natural plant chemicals with anti-cancer potential, but they must be carefully chosen to prevent negative side effects. In this study, the molecular interaction between the breast cancer biomarkers and phytocompound from Dimocarpus longan; and its stability were studied using the molecular docking and dynamic simulation approaches. α-terpineol (ID:442501), corilagin (ID:73568), isoscopoletin (ID:69894), protocatechuic acid (ID:72) and rutin (ID: 5280805) (plant compounds) from longan and estrogen receptor (1ERR) and progesterone receptor (3D90) (target proteins) that were involved in breast cancer were retrieved from the PubChem database and RCSB Protein Data Bank (PDB) respectively. The pharmacokinetics and toxicity analysis of natural compounds were also performed to find a safe and suitable drug for breast cancer treatment using SwissADME and admetSAR tools. Then, The SwissDock server was used to dock them. A molecular dynamics simulation approach was used to determine the stability of the target protein interaction between phytocompound using Gromacs version 4.6.3 software. Corilagin and rutin violated Lipinski's Rule of 5. Moreover, toxicity prediction analysis has demonstrated that α-terpineol did not show any properties that may cause harmful effects to humans when compared with the other four phytocompounds. The docking results show that 1ERR and 3D90 had a negative binding affinity with the α-terpineol at the value of -6.0 and -6.1 kcal/mol respectively. α- terpineol had a stable interaction with 1ERR and 3D90 with the root mean square deviation (RMSD) value of 0.20nm. Therefore, α- terpineol was chosen to use as a safe drug and potential to be a lead compound. It also could be a multi-target inhibitor for estrogen and progesterone receptors. The results of this investigation should help pharmaceutical researchers locate drugs containing longan.
- WHO. 2020. Age-standardized (World) incidence and mortality rates, top 10 cancers. Retrieved January 15, 2021 from https://gco.iarc.fr/today/data/factsheets/populations/458-malaysia-fact-sheets.pdf.Google Scholar
- Zhang X, Guo S, Ho CT, Bai N. 2020. Phytochemical constituents and biological activities of longan (Dimocarpus longan Lour.) fruit: A review. Food Science and Human Wellness 9, 2, 95-102.Google ScholarCross Ref
- Naeem MY. 2020. Medicinal potentials and health benefits of black mulberry. Eurasian Journal of Food Science and Technology 4, 1, 1-5.Google Scholar
- Taghizadeh MS, Niazi A, Moghadam A, Afsharifar A. 2022. Experimental, molecular docking and molecular dynamic studies of natural products targeting overexpressed receptors in breast cancer. Plos One 17, 5, e0267961.Google ScholarCross Ref
- Gurung AB, Ali MA, Lee J, Farah MA, Al-Anazi KM. 2021. Molecular docking and dynamics simulation study of bioactive compounds from Ficus carica L. with important anticancer drug targets. Plos One 216, 7, e0254035.Google Scholar
- Jha V, Devkar S, Gharat K, Kasbe S, Matharoo DK, Pendse S, Bhosale A, Bhargava A. 2022. Screening of phytochemicals as potential inhibitors of breast cancer using structure based multitargeted molecular docking analysis. Phytomedicine Plus 2, 2, 100227.Google ScholarCross Ref
- Kim KH, Young BD, Bender JR. 2014. Endothelial estrogen receptor isoforms and cardiovascular disease. Molecular and Cellular Endocrinology 389, (1-2), 65-70.Google ScholarCross Ref
- Brooks BR, Brooks III CL, Mackerell Jr AD, Nilsson L, Petrella RJ, Roux B, Won Y, Archontis G, Bartels C, Boresch S, Caflisch A. 2009. CHARMM: the biomolecular simulation program. Journal of Computational Chemistry 30, 10, 1545-614.Google ScholarCross Ref
- Lipinski CA. 2004. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discovery Today: Technologies 1, 337-341. https://doi.org/10.1016/j.ddtec.2004.11.007.Google ScholarCross Ref
- Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. 2002. Molecular properties that influence the oral bioavailability of drug candidates. Journal of Medicinal Chemistry 45, 2615-2623. https://doi.org/10.1021/jm020017n.Google ScholarCross Ref
- [Jagtap N, Yadav A, Mohite S. 2020. Synthesis, molecular docking studies and anticancer activity of1,3,4-oxadiazole-3 (2h)-thione derivatives. Journal of University of Shanghai for Science and Technology 22, 535-550.Google Scholar
- Rodrigues J, Hullatti KK, Jalalpure S, Khanal P. 2020. In-vitro Cytotoxicity and in silico Molecular docking of alkaloids from Tiliacora acuminata. Indian Journal of Pharmaceutical Education and Research 54, s295-s300. https://doi.org/10.5530/ijper.54.2s.86.Google ScholarCross Ref
- Tantaw E, Amer A, Mohamed E, Alla M, Nafie M. 2020. Synthesis, characterization of some pyrazine derivatives as anticancer agents: In vitro and in Silico approaches. Journal of Molecular Structure 1210, https://doi.org/10.1016/j.molstruc.2020.128013.Google ScholarCross Ref
- Ikwu F, Shallangwa G, Mamza P. 2020. QSAR, QSTR, and molecular docking studies of the anti-proliferative activity of phenylpiperazine derivatives against DU145 prostate cancer cell lines. Beni-Suef University Journal of Basic and Applied Sciences 9, 1-12. https://doi.org/10.1186/s43088-020-00054-y.Google ScholarCross Ref
- Berman HM, Henrick K, Nakamura H. 2003. Announcing the worldwide Protein Data Bank. Nature Structural Biology 10, 12, 980.Google Scholar
- Jayaram, B. 2011. SCFBIO: What is drug design.Google Scholar
- Grosdidier A, Zoete V, Michielin O. 2011. SwissDock, a protein-small molecule docking web service based on EADock DSS. Nucleic Acids Research 39, W270-277. https://doi.org/10.1093/nar/gkr366.Google ScholarCross Ref
- Abd El-Sattar NEA, El‐Adl K, El-Hashash MA, Salama SA, Elhady MM. 2021. Design, synthesis, molecular docking and in silico ADMET profile of pyrano[2,3-d]pyrimidine derivatives as antimicrobial and anticancer agents. Bioorganic Chemistry 115, https://doi.org/10.1016/j.bioorg.2021.105186.Google ScholarCross Ref
- Parmar DR, Soni JY, Guduru R, Rayani RH, Kusurkar RV, Vala AG, Talukdar SN, Eissa IH, Metwaly AM, Khalil A, Zunjar V. 2021. Discovery of new anticancer thiourea-azetidine hybrids: Design, synthesis, in vitro antiproliferative, SAR, in silico molecular docking against VEGFR-2, ADMET, toxicity, and DFT studies. Bioorganic Chemistry 115, 105206.Google ScholarCross Ref
- Alam S, Nasreen S, Ahmad A, Darokar MP, Khan F. 2021. Detection of natural inhibitors against human liver cancer cell lines through QSAR, molecular docking and ADMET studies. Current Topics in Medicinal Chemistry 21, 8, 686-695.Google Scholar
- Ikwu FA, Shallangwa GA, Mamza PA. QSAR, QSTR, and molecular docking studies of the anti-proliferative activity of phenylpiperazine derivatives against DU145 prostate cancer cell lines. 2020. Beni-Suef University Journal of Basic and Applied Sciences 9, 1, 1-2.Google Scholar
- Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. 2005. GROMACS: fast, flexible, and free. Journal of Computational Chemistry 26, 16, 1701-1718.Google ScholarCross Ref
- Hitchcock SA, Pennington LD. 2006. Structure - Brain Exposure Relationships. Journal of Medicinal Chemistry 49, 26, 7559-7583, doi:10.1021/jm060642i. PMID 17181137.Google ScholarCross Ref
- Smith DA, Di L, Kerns EH. 2010. The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nature Reviews Drug Discovery 9, 929-939, https://doi.org/10.1038/nrd3287.Google ScholarCross Ref
- Garrido A, Lepailleur A, Mignani SM, Dallemagne P, Rochais C. 2020. hERG Toxicity assessment: Useful guidelines for drug design. European Journal of Medicinal Chemistry 195, 112290.Google ScholarCross Ref
- Meyer JN, Leung MC, Rooney JP, Sendoel A, Hengartner MO, Kisby GE. 2013. Mitochondria as a target of environmental toxicants. Toxicology Science 134, 1–17. doi: 10.1093/toxsci/kft102.Google ScholarCross Ref
- [Saravanan R, Raja K, Shanthi D. 2022. GC-MS Analysis, Molecular docking and pharmacokinetic properties of phytocompounds from Solanum torvum unripe fruits and its effect on breast cancer target protein. Applied Biochemistry and Biotechnology 194, 1, 529-555.Google ScholarCross Ref
- Acharya R, Chacko S, Bose P, Lapenna A, Pattanayak SP. 2019. Structure based multitargeted molecular docking analysis of selected furanocoumarins against breast cancer. Scientific Reports 9, 1, 1-3.Google ScholarCross Ref
- Kaur B, Rolta R, Salaria D, Kumar B, Fadare OA, da Costa RA, Ahmad A, Al-Rawi MB, Raish M, Rather IA. 2022. An in silico investigation to explore anti-cancer potential of Foeniculum vulgare Mill. Phytoconstituents for the management of human breast cancer. Molecules 27, 13, 4077.Google ScholarCross Ref
Index Terms
- Pharmacodynamics of Phytocompound from Dimocarpus Longan Against Breast Cancer Biomarkers
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