STRUCTURE-BASED DRUG DESIGN METHOD: MOLECULAR DOCKING STUDY AND PHARMACOPHORE MODELLING OF APIGENIN AS AN ANTIMALARIAL
DOI:
https://doi.org/10.22159/ijap.2023v15i3.47487Keywords:
Antimalarial, Plasmodium falciparum, ApigeninAbstract
Objective: Uses molecular docking and pharmacophore modeling methods to examine the antimalarial activity of apigenin (API) on distinct kinds and varieties of P. falciparum (Pf) receptors.
Methods: Using Autodock 4.0.1 and ligandscout software, molecular docking was conducted on multiple types of Pf receptors, including lactate dehydrogenase (Oxidoreductase), Enoyl-acyl carrier-protein (Oxidoreductase), Triose-phosphate (Isomerase), and plasmepsin II (Hydroxylase).
Results: The lowest free energy binding values found in two of the four investigations (API on an enoyl-acyl carrier and triose-phosphate receptors) suggested a potential effect. These values were-8.06 kcal/mol and-8.76 kcal/mol, respectively. The API had lower values of the inhibitory constant on the lactate dehydrogenase, enoyl-acyl carrier-protein, Triose-phosphate, and plasmepsin II receptors (44.06 µM, 1.24 µM, 376.76 nM, and 57.04 µM, respectively). In terms of the essential elements of amino acid residue interaction, the API and the native ligand were identical (SER218 for 1LF3 receptor; LEU315, GLY110, and TYR111 for 1NWH receptor; VAL212, LYS12, ASN233, and GLY232 for 1O5X receptor; and ILE31, PRO250, and PRO246 for 1U4O receptor). According to the findings of the pharmacophore modeling, the functional groups of hydroxyl were the most important functional groups to interact with the important amino acid residues of the receptors.
Conclusion: The API considerably displays competitive antimalarial potency in various Pf receptors.
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References
World Health Organization. World malaria report; 2022.
Deress T, Girma M. Plasmodium falciparum and Plasmodium vivax prevalence in Ethiopia: a systematic review and meta-analysis. Malar Res Treat. 2019 Des;2019:7065.
Alven S, Aderibigbe B. Combination therapy strategies for the treatment of malaria. Molecules. 2019 Oct;24(19):3601. doi: 10.3390/molecules24193601, PMID 31591293.
Hermanto F, Subarnas A, Sutjiatmo AB, Berbudi A. Apigenin: review of mechanisms of action as antimalarial. Res J Pharm Technol. 2022 Jan:458-66. doi: 10.52711/0974-360X.2022.00075.
Salehi B, Venditti A, Sharifi Rad M, Kręgiel D, Sharifi Rad J, Durazzo A. The therapeutic potential of Apigenin. Int J Mol Sci. 2019 Mar;20(6):1305. doi: 10.3390/ijms20061305, PMID 30875872.
El-bassossy HM, Desoky N, Alahdal AM, Fahmy A. Normal vascular reactivity is restored by apigenin in diabetic rats. Int J Pharm Pharm Sci. 2018 Jan;10(1):27-31. doi: 10.22159/ijpps.2018v10i1.16621.
Perozzo R, Kuo M, Sidhu ABS, Valiyaveettil JT, Bittman R, Jacobs WR. Structural elucidation of the specificity of the antibacterial agent triclosan for malarial enoyl acyl carrier protein reductase. J Biol Chem. 2002 Apr;277(15):13106-14. doi: 10.1074/jbc.M112000200, PMID 11792710.
Nunes RR, Fonseca ALD, Pinto ACS, Maia EHB, Silva AMD, Varotti FP. Brazilian malaria molecular targets (BraMMT): selected receptors for virtual high-throughput screening experiments. Mem Inst Oswaldo Cruz. 2019;114:e180465. doi: 10.1590/0074-02760180465. PMID 30810604.
Asojo OA, Gulnik SV, Afonina E, Yu B, Ellman JA, Haque TS. Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from plasmodium falciparum. J Mol Biol. 2003 Mar;327(1):173-81. doi: 10.1016/s0022-2836(03)00036-6, PMID 12614616.
Morris GM, Huey R, Olson AJ. Using autodock for ligand-receptor docking. Curr Protoc Bioinformatics. 2008 Dec;8:14. doi: 10.1002/0471250953.bi0814s24, PMID 19085980.
Bhowmik R, Roy S, Sengupta S, Sharma S. Biocomputational and pharmacological analysis of phytochemicals from Zingiber officinale (Ginger), Allium sativum (garlic), and murrayakoenigii (curry leaf) in contrast to type 2-diabetes. Int J App Pharm. 2021;13(5):280-6. doi: 10.22159/ijap.2021v13i5.42294.
Parthasarathy S, Eaazhisai K, Balaram H, Balaram P, Murthy MRN. Structure of Plasmodium falciparum triose-phosphate isomerase-2-phosphoglycerate complex at 1.1-Å resolution. J Biol Chem. 2003 Dec;278(52):52461-70. doi: 10.1074/jbc.M308525200, PMID 14563846.
Morris GM, Huey R, Olson AJ. Using AutoDock for ligand-receptor docking. Curr Protoc Bioinformatics. 2008;Chapter(8):Unit8.14. doi: 10.1002/0471250953.bi0814s24.PMID 19085980.
Langer T, Hoffmann RD. Pharmacophore modelling: applications in drug discovery. Expert Opin Drug Discov. 2006 Aug;1(3):261-7. doi: 10.1517/17460441.1.3.261, PMID 23495846.
Caporuscio F, Tafi A. Pharmacophore modelling: a forty year old approach and its modern synergies. Curr Med Chem. 2011 Jun;18(17):2543-53. doi: 10.2174/092986711795933669, PMID 21568893.
Mountzios G, Kostopoulos I, Kotoula V, Sfakianaki I, Fountzilas E, Markou K. In silico analysis of dietary agents as anticancer inhibitors of insulin like growth factor 1 receptor (igf1r). Int J Pharm Pharm Sci. 2015 Sep;8(1):191-6.
Bissantz C, Kuhn B, Stahl M. A medicinal chemist’s guide to molecular interactions. J Med Chem. 2010;53(14):5061-84. doi: 10.1021/jm100112j, PMID 20345171.
Djajadisastra J, Purnama HD, Yanuar A. In silico binding interaction study of mefenamic acid and piroxicam on human albumin. Int J Appl Pharm. 2017;9(5):102-6.
Niu Y, Liu R, Guan C, Zhang Y, Chen Z, Hoerer S. Structural basis of inhibition of the human SGLT2–MAP17 glucose transporter. Nature. 2022;601(7892):280-4. doi: 10.1038/s41586-021-04212-9, PMID 34880493.
Cournia Z, Allen B, Sherman W. Relative binding free energy calculations in drug discovery: recent advances and practical considerations. J Chem Inf Model. 2017;57(12):2911-37. doi: 10.1021/acs.jcim.7b00564, PMID 29243483.
Luo H, Fokoue Nkoutche A, Singh N, Yang L, Hu J, Zhang P. Molecular docking for prediction and interpretation of adverse drug reactions. Comb Chem High Throughput Screen. 2018;21(5):314-22. doi: 10.2174/1386207321666180524110013, PMID 29792141.
Niu Y, Liu R, Guan C, Zhang Y, Chen Z, Hoerer S. Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature. 2022 Jan;601(7892):280-4. doi: 10.1038/s41586-021-04212-9, PMID 34880493.
Cournia Z, Allen B, Sherman W. Relative binding free energy calculations in drug discovery: recent advances and practical considerations. J Chem Inf Model. 2017 Dec;57(12):2911-37. doi: 10.1021/acs.jcim.7b00564, PMID 29243483.
Luo H, Fokoue Nkoutche A, Singh N, Yang L, Hu J, Zhang P. Molecular docking for prediction and interpretation of adverse drug reactions. Comb Chem High Throughput Screen. 2018 May;21(5):314-22. doi: 10.2174/1386207321666180524110013, PMID 29792141.
Muchtaridi M, Syahidah HN, Subarnas A, Yusuf M, Bryant SD, Langer T. Molecular docking and 3D-pharmacophore modeling to study the interactions of chalcone derivatives with estrogen receptor alpha. Pharmaceuticals (Basel). 2017;10(4):81. doi: 10.3390/ph10040081, PMID 29035298.
Opoku F, Govender PP, Pooe OJ, Simelane MBC. Evaluating iso-mukaadial acetate and ursolic acid acetate as plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase inhibitors. Biomolecules. 2019;9(12):861. doi: 10.3390/biom9120861, PMID 31835879.
Han HS, Kang G, Kim JS, Choi BH, Koo SH. Regulation of glucose metabolism from a liver-centric perspective. Exp Mol Med. 2016 Mar 4;48(3):e218. doi: 10.1038/emm.2015.122, PMID 26964834.
Bissantz C, Kuhn B, Stahl M. A medicinal chemist’s guide to molecular interactions. J Med Chem. 2010 Jul 22;53(14):5061-84. doi: 10.1021/jm100112j, PMID 20345171.
Ravichandran S, Singh N, Donnelly D, Migliore M, Johnson P, Fishwick C. Pharmacophore model of the quercetin binding site of the SIRT6 protein. J Mol Graph Model. 2014 Apr;49:38-46. doi: 10.1016/j.jmgm.2014.01.004, PMID 24491483.
Seeliger D, De Groot BL. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J Comput Aided Mol Des. 2010 May;24(5):417-22. doi: 10.1007/s10822-010-9352-6, PMID 20401516.
Morozov AV, Kortemme T. Potential functions for hydrogen bonds in protein structure prediction and design. Adv Protein Chem. 2005;72:1-38. doi: 10.1016/S0065-3233(05)72001-5, PMID 16581371.
Matta CF, Hernandez Trujillo J, Tang TH, Bader RFW. Hydrogen–hydrogen bonding: a stabilizing interaction in molecules and crystals. Chemistry. 2003 May;9(9):1940-51. doi: 10.1002/chem.200204626, PMID 12740840.
Kumar S, Khatik GL, Mittal A. In silico molecular docking study to search new SGLT2 inhibitor based on dioxabicyclo[3.2.1] octane scaffold. Curr Comput Aided Drug Des. 2020;16(2):145-54. doi: 10.2174/1573409914666181019165821. PMID 30345926.
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