MOLECULAR DOCKING AND PHARMACOKINETIC PREDICTION OF HERBAL DERIVATIVES AS MALTASE-GLUCOAMYLASE INHIBITOR
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i9.19337Keywords:
Absorption, distribution, metabolism, excretion, and toxicity, Herbal derivatives, Maltase-glucoamylase, Molecular docking, PharmacokineticsAbstract
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 Objective: To perform molecular docking and pharmacokinetic prediction of momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine herbal derivatives as maltase-glucoamylase (MGAM) inhibitors for the treatment of diabetes.
Methods: The herbal derivatives and standard drug miglitol were docked differently onto MGAM receptor using AutoDock Vina software. In addition, Lipinski's rule, drug-likeness, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties were analyzed using Molinspiration, ADMET structure–activity relationship, and prediction of activity spectra for substances online tools.
Results: Docking studies reveal that momordicoside F2, beta-sitosterol, and cis-N-feruloyltyramine derivatives have high binding affinity to the MGAM receptor (−7.8, −6.8, and −6.5 Kcal/Mol, respectively) as compared to standard drug miglitol (−5.3 Kcal/Mol). In addition, all the herbal derivatives indicate good bioavailability (topological polar surface area <140 Ȧ and Nrot <10) without toxicity or mutagenic effects.
Conclusion: The molecular docking and pharmacokinetic information of herbal derivatives obtained in this study can be utilized to develop novel MGAM inhibitors having antidiabetic potential with better pharmacokinetic and pharmacodynamics profile.
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Bang H, Edwards AM, Bomback AS, Ballantyne CM, Brillon D, Callahan MA, et al. Development and validation of a patient self-assessment score for diabetes risk. Ann Intern Med 2009;151(11):775-83.
Hamman RF. Genetic and environmental determinants of non-insulin-dependent diabetes mellitus (NIDDM). Diabetes Metab Rev 1992;8(4):287-338.
Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010;87(1):4-14.
Encina G, Ezquer F, Conget P, Israel Y. Insulin is secreted upon glucose stimulation by both gastrointestinal enteroendocrine K-cells and L-cells engineered with the preproinsulin gene. Biol Res 2011;44(3):301-5.
Cade WT. Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Phys Ther 2008;88(11):1322-35.
Zhang BB, Moller DE. New approaches in the treatment of type 2 diabetes. Curr Opin Chem Biol 2000;4(4):461-7.
Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: A new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58(4):773-95.
Mooradian AD, Thurman JE. Drug therapy of postprandial hyperglycaemia. Drugs 1999;57(1):19-29.
Krentz AJ, Bailey CJ. Oral antidiabetic agents: Current role in type 2 diabetes mellitus. Drugs 2005;65(3):385-411.
Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44) Diabetes Care 1999;22(6):960-4.
Tugrul S, Kutlu T, Pekin O, Baglam E, Kiyak H, Oral O. Clinical, endocrine, and metabolic effects of acarbose, a alpha-glucosidase inhibitor, in overweight and nonoverweight patients with polycystic ovarian syndrome. Fertil Steril 2008;90(4):1144-8.
Asano N. Glycosidase inhibitors: Update and perspectives on practical use. Glycobiology 2003;13(10):93R-104R.
Bischoff H. Pharmacology of R-glucosidase inhibition. Eur J Clin Invest 1994;18(4):243-10.
Toeller M. Nutritional recommendations for diabetic patients and treatment with alpha-glucosidase inhibitors. Drugs 1992;44 Suppl 3:13-20.
Li C, Begum A, Numao S, Park KH, Withers SG, Brayer GD. Acarbose rearrangement mechanism implied by the kinetic and structural analysis of human pancreatic alpha-amylase in complex with analogues and their elongated counterparts. Biochemistry 2005;44(9):3347-57.
Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR. Human intestinal maltase-glucoamylase: Crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol 2008;375(3):782-92.
Liu H, Nasi R, Jayakanthan K, Sim L, Heipel H, Rose DR, et al. New synthetic routes to chain-extended selenium, sulfur, and nitrogen analogues of the naturally occurring glucosidase inhibitor salacinol and their inhibitory activities against recombinant human maltase glucoamylase. J Org Chem 2007;72(17):6562-72.
Kaur R, Afzal M, Kazmi I, Ahamd I, Ahmed Z, Ali B, et al. Polypharmacy (herbal and synthetic drug combination): A novel approach in the treatment of type-2 diabetes and its complications in rats. J Nat Med 2013;67(3):662-71.
Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - Validation of the Ayurvedic pharmacology through experimental and clinical studies. Int J Ayurveda Res 2010;1(8):112-21.
Lo HY, Ho TY, Lin C, Li CC, Hsiang CY. Momordica charantia and its novel polypeptide regulate glucose homeostasis in mice via binding to insulin receptor. J Agric Food Chem 2013;61(10):2461-8.
Chen Q, Chan LL, Li ET. Bitter melon (Momordica charantia) reduces adiposity, lowers serum insulin and normalizes glucose tolerance in rats fed a high fat diet. J Nutr 2003;133(4):1088-93.
Chang CL, Lin Y, Bartolome AP, Chen YC, Chiu SC, Yang WC. Herbal therapies for type 2 diabetes mellitus: Chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat Med 2013;2013(2):378657.
Rupeshkumar M, Kavitha K, Haldar PK. The role of herbal plants in the diabetes mellitus therapy: An overview. Int J Appl Pharm 2014;6(3):1-3.
Bhavesh CV, Siddharth JM, Jignasa KS, Snehal SP. In silico molecular docking and pharmacokinetic prediction of gallic acid herbal derivatives as ppar-γ agonists. Int J Pharm Pharm Sci 2017;9(1):102-7.
Punabaka J, Kuna Y. Molecular docking studies on the therapeutic targets of Alzheimer disease (AChE and BChE) using natural bioactive alkaloids. Int J Pharm Pharm Sci 2016;8(12):108-12.
Akshada J, Manoj G, Urmila JJ. Identification of potential novel EGFR inhibitors using a combination of pharmacophore and docking methods. Int J Pharm Pharm Sci 2015;7(6) 77-91.
Klebe G. Recent developments in structure-based drug design. J Mol Med (Berl) 2000;78(5):269-81.
Tollenaere JP. The role of structure-based ligand design and molecular modelling in drug discovery. Pharm World Sci 1996;18(2):56-62.
Anderson AC. The process of structure-based drug design. Chem Biol 2003;10(9):787-97.
Jorgensen WL. The many roles of computation in drug discovery. Science 2004;303(5665):1813-8.
Schneider G, Fechner U. Computer-based de novo design of drug-like molecules. Nat Rev Drug Discov 2005;4:649-63.
Ochieng PJ, Kusuma WA, Rafi M, Sumaryada T. Deciphering the action mechanism of Indonesia herbal decoction in the treatment of type II diabetes using a network pharmacology approach. Int J Pharm Pharm Sci 2017;9(3):243-53.
Wang Y, Xiao J, Suzek TO, Zhang J, Wang J, Bryant SH. PubChem: A public information system for analyzing bioactivities of small molecules. Nucleic Acids Res 2009;37(Web Server issue):W623-33.
Laskowski RA, Hutchinson EG, Michie AD, Wallace AC, Jones ML, Thornton JM. PDBsum: A Web-based database of summaries and analyses of all PDB structures. Trends Biochem Sci 1997;22(12):488-90.
Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31(2):455-61.
Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem 2009;30(16):2785-91.
Sherman W, Day T, Jacobson MP, Friesner RA, Farid R. Novel procedure for modeling ligand/receptor induced fit effects. J Med Chem 2006;49(2):534-53.
Schnecke V, Kuhn LA. Virtual screening with solvation and ligand-induced complementarity. Perspect Drug Discov Design 2000;20(1):171-90.
Laskowski RA, Swindells MB. LigPlot+: Multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model 2011;51(10):2778-86.
Perola E, Walters WP, Charifson PS. A detailed comparison of current docking and scoring methods on systems of pharmaceutical relevance. Proteins 2004;56(2):235-49.
Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, et al. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 2012;52(11):3099-105.
Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 2000;43:3714-7.
Lipinski CA. Lead-and drug-like compounds: The rule-of-five revolution. Drug Discov Today Technol 2004;1(4):337-41.
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001;46(1-3):3-26.
Lagunin A, Stepanchikova A, Filimonov D, Poroikov V. PASS: Prediction of activity spectra for biologically active substances. Bioinformatics 2000;16(8):747-8.
Warren GL, Warren SD. Scoring drug-receptor interaction. In: Gramatica P, Livingstone DJ, Davis AM. Drug Design Strategies: Quantitative Approaches. Ch. 16, Vol. 440. Cambridge U.K.: Royal Society Chemistry: 2011. p. 57.
Yuan Y, Pei J, Lai L. Binding site detection and druggability prediction of protein targets for structure-based drug design. Curr Pharm Des 2013;19(12):2326-33.
Leis S, Schneider S, Zacharias M. In silico prediction of binding sites on proteins. Curr Med Chem 2010;17(15):1550-62.
Sim L, Jayakanthan K, Mohan S, Nasi R, Johnston BD, Pinto BM, et al. New glucosidase inhibitors from an ayurvedic herbal treatment for type 2 diabetes: Structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata. Biochemistry 2010;49(3):443-51.
Ren L, Qin X, Cao X, Wang L, Bai F, Bai G, et al. Structural insight into substrate specificity of human intestinal maltase-glucoamylase. Protein Cell 2011;2(10):827-36.
Sim L, Willemsma C, Mohan S, Naim HY, Pinto BM, Rose DR. Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. J Biol Chem 2010;285(23):17763-70.
Balani SK, Miwa GT, Gan LS, Wu JT, Lee FW. Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection. Curr Top Med Chem 2005;5(11):1033-8.
Tetko IV, Bruneau P, Mewes HW, Rohrer DC, Poda GI. Can we estimate the accuracy of ADME-Tox predictions? Drug Discov Today 2006;11(15-16):700-7.
Yu H, Adedoyin A. ADME-Tox in drug discovery: Integration of experimental and computational technologies. Drug Discov Today 2003;8(18):852-61.
Singh SS. Preclinical pharmacokinetics: An approach towards safer and efficacious drugs. Curr Drug Metab 2006;7(2):165-82.
Srimai V, Ramesh M, Satya PK, Parthasarathy T. Computer-aided design of selective cytochrome P450 inhibitors and docking studies of alkylresorcinol derivatives. Med Chem Res 2013;22(4):5314-23.
Chang LC, Spanjersberg RF, von Frijtag Drabbe Künzel JK, Mulder-Krieger T, van den Hout G, Beukers MW, et al. 2,4,6-trisubstituted pyrimidines as a new class of selective adenosine A1 receptor antagonists. J Med Chem 2004;47(26):6529-40.
Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 2002;45(12):2615-23.
Lynch T, Price A. The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 2007;76(3):391-6.
Sharom FJ. The P-glycoprotein efflux pump: How does it transport drugs? J Membr Biol 1997;160(3):161-75.
Verma N, Amresh G, Sahu PK, Rao ChV, Singh AP. Antihyperglycemic and antihyperlipidemic activity of ethyl acetate fraction of Rhododendron arboreum Smith flowers in streptozotocin induced diabetic rats and its role in regulating carbohydrate metabolism. Asian Pac J Trop Biomed 2012;2(9):696-701.
Madar Z. The effect of acarbose and miglitol (BAY-M-1099) on postprandial glucose levels following ingestion of various sources of starch by nondiabetic and streptozotocin-induced diabetic rats. J Nutr 1989;119(12):2023-9.
Bischoff H. The mechanism of alpha-glucosidase inhibition in the management of diabetes. Clin Invest Med 1995;18(4):303-11.
Tadera K, Minami Y, Takamatsu K, Matsuoka T. Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J Nutr Sci Vitaminol (Tokyo) 2006;52(2):149-53.
Mayor F Jr., Lucas E, Jurado-Pueyo M, Garcia-Guerra L, Nieto-Vazquez I, Vila-Bedmar R, et al. G Protein-coupled receptor kinase 2 (GRK2): A novel modulator of insulin resistance. Arch Physiol Biochem 2011;117(3):125-30.
Shahid G, Hussain T. GRK2 negatively regulates glycogen synthesis in mouse liver FL83B cells. J Biol Chem 2007;282(28):20612-20.
Carotenuto A, Cipolletta E, Gomez-Monterrey I, Sala M, Vernieri E, Limatola A, et al. Design, synthesis and efficacy of novel G protein-coupled receptor kinase 2 inhibitors. Eur J Med Chem 2013;69(8):384-92.
Jerad SA, Devi R, Noorulla KM, Surya PR. Insights into thioridazine for its anti-tubercular activity from molecular docking studies. Int J Pharm Pharm Sci 2015;7(3):344-6.
Usui I, Imamura T, Satoh H, Huang J, Babendure JL, Hupfeld CJ, et al. GRK2 is an endogenous protein inhibitor of the insulin signaling pathway for glucose transport stimulation. EMBO J 2004;23(14):2821-9.
Homan KT, Tesmer JJ. Molecular basis for small molecule inhibition of G protein-coupled receptor kinases. ACS Chem Biol 2015;10(1):246-56.
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