Quantum Chemical Computations, Molecular Docking, and ADMET Predictions of Cynarin

Yıl 2024, Cilt: 13 Sayı: 2, 460 - 466, 29.06.2024

Sevtap Çağlar Yavuz

https://doi.org/10.17798/bitlisfen.1425717

Öz

Cynarin (1,3-o-dicaffeoylquinic acid) is one of the biologically active functional food components which is the most well-known caffeoylquinic acid derivative found in artichoke. The structural and electronic features of cynarin compound were investigated theoretically using density functional theory (DFT). The highest occupied molecular orbital (HOMO) and the least occupied molecular orbital (LUMO) are the most significant orbitals in molecules, these orbitals are quite helpful to know several molecular features such as the chemical reactivity, kinetic stability, electronegativity, chemical potential, electrophilicity index, chemical hardness and softness and electronegativity. Molecular orbital analysis HOMO-LUMO was used to explore the stability of the molecule. Moreover, physicochemical properties, drug-likeness, and toxicity estimation of the cynarin compound were appraised owing to ADMET (including absorption, distribution, metabolism, excretion, and toxicology). Molecular docking was carried out to examine the biological activity of the cynarin compound. 5A19, a liver cancer biomarker, is human methionine adenosyl-transferase enzymes. Cynarin-methionine adenosyl-transferase enzyme binding energy value was calculated as -7.9 kcal/mol. As a result, this in silico study confirmed that cynarin has the potential to be a drug by revealing its protective effect against liver diseases.

Anahtar Kelimeler

Cynarin, DFT, HOMO-LUMO, Molecular docking, Spartan

Kaynakça

• [1] M. J. Wargovich, “Experimental evidence for cancer preventive elements in foods,” Cancer Lett, vol. 114, no. 1-2, pp. 11-17, 1997.
• [2] S. Bekheet and V. Sota, “Biodiversity and medicinal uses of globe artichoke (Cynara scolymus L.) plant,” J Biodivers Conserv Bioresour Manag, vol. 5, no. 1, pp. 39-54, 2019.
• [3] H. O. Santos, A. A. Bueno, J. F. Mota, “The effect of artichoke on lipid profile: A review of possible mechanisms of action,” Pharmacol Res, vol. 137, pp. 170-178, 2018.
• [4] M. Wang, J. E. Simon, I. F. Aviles, K. He, Q. Y. Zheng, Y. Tadmor, “Analysis of antioxidative phenolic compounds in artichoke (Cynara scolymus L.),” J Agric Food Chem, vol. 51, no. 3, pp. 601-608, 2003.
• [5] M. A. Farag, S. H. El-Ahmady, F. S. Elian, L. A. Wessjohann, “Metabolomics driven analysis of artichoke leaf and its commercial products via UHPLC–q-TOF-MS and chemometrics,” Phytochemistry, vol. 95, pp. 177-187, 2013.
• [6] N. F. Hassabou, and A. F. Farag, “Anticancer effects induced by artichoke extract in oral squamous carcinoma cell lines,” J Egypt Natl Canc Inst, vol. 32, no. 1, pp. 1-10. 2020.
• [7] R. Llorach, J. C. Espin, F. A. Tomas-Barberan, F. Ferreres, “Artichoke (Cynara scolymus L.) byproducts as a potential source of health-promoting antioxidant phenolics,” J Agric Food Chem, vol. 50, no. 12, pp. 3458-3464, 2002.
• [8] G. Löhr, A. Deters, A. Hensel, “In vitro investigations of Cynara scolymus L. extract on cell physiology of HepG2 liver cells,” Braz J Pharm Sci, vol. 45, pp. 201-208, 2009.
• [9] E. Speroni, R. Cervellati, P. Govoni, S. Guizzardi, C. Renzulli, M. C. Guerra, “Efficacy of different Cynara scolymus preparations on liver complaints,” J Ethnopharmacol, vol. 86, no. 2-3, pp. 203-211, 2003.
• [10] E. Christaki, E. Bonas, P. Floray-Paneri, “Nutritional And Functional Properties of Cynara Crops (Clobe Artichoke and Cardoon) and Their Potential Applications: A Review,” Int J Appl Sci Technol, vol. 2, no. 2, pp. 64-68, 2012.
• [11] S. C. Lu, L. Alvarez, Z. Z. Huang, L. Chen, W. An, F. J. Corrales, M. A. Avila, G. Kanel, J. M. Mato, “Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation,” Proc Natl Acad Sci, vol. 98, no. 10, pp. 5560-5565, 2001.
• [12] G. Sliwoski, S. Kothiwale, J. Meiler, E. W. Lowe, “Computational methods in drug discovery,” Pharmacol Rev, vol. 66, no. 1, pp. 334-395, 2014.
• [13] H. J. Liao and J. T. Tzen, “The potential role of phenolic acids from Salvia miltiorrhiza and Cynara scolymus and their derivatives as JAK inhibitors: An in silico study,” Int J Mol Sci, vol. 23, no. 7, pp. 4033, 2022.
• [14] M. H. Malekipour, F. Shirani, S. Moradi, A. Taherkhani, “Cinnamic acid derivatives as potential matrix metalloproteinase-9 inhibitors: molecular docking and dynamics simulations,” Genom Inform, vol. 21, no. 1, pp. e9, 2023.
• [15] G. AbrahamDogo, O. Uchechukwu, U. Umar, A. J. Madaki, J. C. Aguiyi, “Molecular docking analyses of phytochemicals obtained from African antiviral herbal plants exhibit inhibitory activity against therapeutic targets of SARS-CoV-2,” Res Sq, pp. 1-15. 2020.
• [16] M. Villarini, M. Acito, R. di Vito, S. Vannini, L. Dominici, C. Fatigoni, R. Pagiotti, M. Moretti, “Pro-apoptotic activity of artichoke leaf extracts in human HT-29 and RKO colon cancer cells,” Int J Environ Res Public Health, vol. 18, no. 8, pp. 4166, 2021.
• [17] D. B. Kim, B. Unenkhuu, G. J. Kim, S.W. Kim, H. S. Kim, “Cynarin attenuates LPS-induced endothelial inflammation via upregulation of the negative regulator MKP-3. Animal Cells and Systems,” vol. 26, no. 3, 119-128, 2022.
• [18] E. N. Simsek and T. Uysal, “In vitro investigation of cytotoxic and apoptotic effects of Cynara L. species in colorectal cancer cells,” Asian Pac J Cancer, vol. 14, no. 11, pp. 6791-6795, 2013.
• [19] P. G. Seybold, “Quantum chemical estimation of the acidities of some inorganic oxoacids,” Mol Phys, vol. 113, no. 3-4, pp. 232-236, 2015.
• [20] S. S. Butt, Y. Badshah, M. Shabbir, M. Rafiq, “Molecular docking using chimera and autodock vina software for nonbioinformaticians,” JMIR Bioinfor Biotech, vol. 1, no. 1, pp. e14232, 2020.
• [21] R. Al-Ghani, W. P. Nirwani, T. N. Novianti, A. G. P. Sari, “In silico anti-inflammatory activity evaluation from usnea misaminensis through molecular docking approach,” Chem Mater, vol. 1, no. 3, pp. 77-82, 2022.
• [22] S. C. Yavuz, “Theoretical electronic properties, Admet prediction, and molecular docking studies of some imidazole derivatives,” J Sci Rep A, vol. 51, pp. 340-357, 2022.
• [23] A. Yiğit and Z. S. Turhan, “Theoretical Investigation of some synthesized 3-arylamino-5-[2-(substituted 1-imidazole) ethyl 1]-1, 2, 4-triazole derivatives,” Yuzuncu Yil University J Inst Nat Appl Sci, vol. 28, no. 1, pp. 76-91, 2023.
• [24] P. W. Atkins and J. de Paula, Physical chemistry for the life sciences, Oxford, England: W. H. Freeman, 2006.
• [25] P. T. Tasli, T. Soganci, S. O. Kart, H. H. Kart, M. Ak, “Quantum mechanical calculations of different monomeric structures with the same electroactive group to clarify the relationship between structure and ultimate optical and electrochemical properties of their conjugated polymers,” J Phys Chem Solids, vol. 149, pp. 109720, 2021.
• [26] J. S. Murray and P. Politzer, “The electrostatic potential: an overview,” Wiley Interdiscip Rev Comput Mol Sci, vol. 1, no. 2, pp. 153-163, 2011.
• [27] P. Jayaprakash, M. L. Caroline, S. Sudha, R. Ravisankar, G. Vinitha, P. Ramesh, E. Raju, “Synthesis, growth, optical and third order nonlinear optical properties of l-phenylalanine d-mandelic acid single crystal for photonic device applications,” J Mater Sci Mater Electron, vol. 31, pp. 20460-20471, 2020.
• [28] F. C. Asogwa, U. D. Izuchukwu, H. Louis, C. C. Eze, C. M. Ekeleme, J. A. Ezugwu, I. Benjamin, S. I. Attah, E. C. Agwamba, O. C. Ekoh, A. S. Adeyinka, “Synthesis, characterization and theoretical investigations on the molecular structure, electronic property and anti-trypanosomal activity of benzenesulphonamide-based carboxamide and its derivatives,” Polycycl Aromat Comp, vol. 43, no. 10, pp. 8690-8709, 2023.
• [29] Dassault Systèmes BIOVIA, Discovery studio visualizer. v16.1.0.15350, San Diego: Dassault Systèmes, 2016.
• [30] A. Daina, O. Michielin, V. Zoete, “SwissADME: A free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules,” Sci Rep, vol. 7, pp. 42717-42729, 2017.
• [31] C. A Lipinski, F. Lombardo, B. W. Dominy, P. J. Feeney, “Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings,” Adv Drug Deliv Rev, vol. 46, no.1–3, pp. 3–26, 2001.
• [32] B. E. Oyinloye, T. A. Adekiya, R. T. Aruleba, O. A. Ojo, B. O. Ajiboye, “Structure-based docking studies of GLUT4 towards exploring selected phytochemicals from Solanum xanthocarpum as a therapeutic target for the treatment of cancer,” Curr Drug Discov Technol. vol. 16, no. 4, pp. 406-416, 2019.
• [33] F. P, Guengerich, J. S. MacDonald, “Applying mechanisms of chemical toxicity to predict drug safety,” Chem Res Toxicol, vol. 20, no. 3, pp. 344-369, 2007