In Silico Design & Development of Some Selected Flavonols Against Beta–Glucuronidase Inhibitory Activity
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Keywords

Protein ligand
β-glucuronidase
serum acid
Chromen
binding affinity

How to Cite

Sovan Pattanaik, Sudam Chandra Si, Sudhanshu Sekhar Rout, Anindya Bose, & Siva Shankar Nayak. (2015). In Silico Design & Development of Some Selected Flavonols Against Beta–Glucuronidase Inhibitory Activity. Journal of Pharmacy and Nutrition Sciences, 5(1), 43–49. https://doi.org/10.6000/1927-5951.2015.05.01.7

Abstract

Drug discovery process develops faster due to more advances in computational techniques. The protein ligand interaction well predicted due to the in-silico approach study. The present investigation focused towards the development of lead structure for treatment of hepatic disorders. An increase in serum acid hydrolase, including β-glucuronidase has been reported in numbers of pathological conditions such as arthritis, renal diseases and epilepsies. Enhancement of this enzyme β–glucuronidase in blood has been found to correlate significantly with liver damage. β-glucuronidase inhibitor is a novel approach which is different from the available hepatoprotective drug therapies.

Method: The current study is based on in-silico ligand screening and in-vitro estimation of the three flavonols [Naringenin, Quercetin and 2-(3, 4-Dihydroxy Phenyl)-7-Hydroxy-3-(2-Hydroxy Ethoxy) 4-H-Chromen-4one] compounds with enzyme β-glucuronidase. Molecular docking software Py Rex and Py Mol was used to dock the selected ligand in the binding site of the crystal structure of protein.

Results: Docking results are based on the least binding energy of the selected flavonols compounds. Further attempt has been made towards in-vitro estimation of this enzyme with those selected compounds. The binding affinity with existence of hydrogen bonds leads to find out the mechanism which was well correlated with the findings of in-vitro inhibitory activity.

Conclusion: The result outcome of the binding orientation of 2-(3, 4-Dihydroxy Phenyl)-7-Hydroxy-3-(2-Hydroxy Ethoxy) 4-H-Chromen-4one linked with the active amino acid residue of the protein and the binding affinity leads to find out the mechanism for its potential in-vitro inhibitory activity.

https://doi.org/10.6000/1927-5951.2015.05.01.7
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References

Pattanaik S, Panda J, Sahu PK, Banerjee MB, Rout SS. Synthesis characterization and biological evaluation of bidentate ligands (Reduced Schiff?s base) with metals of copper, nickel and Zinc complexes. Rasayan J of Chemistry 2006; 5: 136-141.

Paul D. Structure-based virtual screening: an overview. DDT 2002; 720: 1047-1055.

Rarey M, Kramer B, Lengauer T, Klebe G. A fast flexible docking method using an incremental construction algorithm. J Mol Biol 1996; 261: 470-489. http://dx.doi.org/10.1006/jmbi.1996.0477

Verschoyle RD, Steward WP, Gescher AJ. Putative cancer chemo preventive agents of dietary origin-how safe are they? Nature Cancer 2007; 59: 152-162.

Rout SS, Pattanaik S, Si SC, Pal A, Sahoo RN, Mohanty P. Anti-Nociceptive activities of complexes of Naringin with CO (II) metal ions. Int J Pharm Pharm. Sci 2013; 5: 972-975.

Rietjens IM, Boersma MG, van der Woude H, Jeurissen SM, Schutte ME, Alink GM. Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk. Mutat Res 2005; 574: 124-138. http://dx.doi.org/10.1016/j.mrfmmm.2005.01.028

Pattanaik S, Si SC, Rout SS, Nayak SS. Evaluation of hepatoprotective and lipid peroxidation activity of the plant Crataeva magna Buch Ham (Capparidaceae). Der Pharmacia Lettre 2013; 5: 333-337.

Stahl PD, Fishman WH. ?-D-glucuronidase, In: Method of Enzymatic Analysis. (Ed. Bergmeyer HU), 3rd ed., Weinheim, Verlag Chemie 1984; p. 246-256.

Pineda EP, Goldberg JA, Banks BM, Rutenburg AM. The significance of serum ?-glucuronidase activity in patients with liver disease. Gastroenterology 1959; 36: 202-213.

Mills GT, Smith EEB. The 3-glucuronidase activity of chemically induced rat hepatoma. Science 1951; 114: 690-692. http://dx.doi.org/10.1126/science.114.2974.690

Levy GA, Kerr LMH, Campbell JC. ?-Glucuronidase and cell proliferation. Biochem J 1948; 42: 462-468.

Mills GT, Paul J, Smith EE. Studies in beta-glucuronidase. III. The influence of age, partial hepatectomy and other factors in the ?-glucuronidase activity in rat liver. Biochem J 1953; 53: 245-253.

Pattanaik S, Si SC, Pal A, Nayak SS. Evaluation of hepatoprotectve activity and isolation of 2-(3, 4-dihydroxy phenyl)-7-hydroxy-3-(2-hydroxy ethoxy) 4-H-chromen-4one from column fractions of leaves of the extract of Crataeva magna. Int. J Phytomedicine 2013; 5: 452-459.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acid Res 2000; 28: 235-242. http://dx.doi.org/10.1093/nar/28.1.235

Jain S, Drendel WB, Chen JW, Mathews FS, Sly WS, Grub JH. Structure of beta-glucuronidase reveals lysosomal targeting and active site motifs. Nat. Str. Biol 1996; 3: 375-381. http://dx.doi.org/10.1038/nsb0496-375

Lipinski CA. Lead- and drug-like compounds. Drug Discov Today Technol 2004; 1: 337-341. http://dx.doi.org/10.1016/j.ddtec.2004.11.007

Lipinski CA, Lombardo F, Doming BV, Feenay PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46: 3-26. http://dx.doi.org/10.1016/S0169-409X(00)00129-0

Kumar DB, Kumar PV, Bhubaneswaran SP, Mitra A. Advanced drug designing softwares and their application in medical research. Int J Pharm Pharm Sci 2010; 2: 16-18.

Daisy P, Nivedha RP, Bakiya RH. In silico drug designing approach for biotin protein ligase of Mycobacterium tuberculosis. Asian J Pharm Clin Res 2013; 6: 103-107

Sekikawa C, Kurihara H, Goto K, Takahashi K. Inhibition of beta-Glucuronidase by Extracts of Chondria crassicaulis. Bull Fish Sci Hokkaido Univ 2002; 53: 27-30.

Khan KM, Rahim F, Halim SA, Taha M, Khana M, Perveen S, Zaheer-ul-Haq, Mesaik MA, Choudhary MI. Synthesis of novel inhibitors of beta-glucuronidase based on benzothiazole skeleton and study of their binding affinity by molecular docking. Bioorganic & Medicinal Chemistry 2011; 19: 4286-4294. http://dx.doi.org/10.1016/j.bmc.2011.05.052

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Copyright (c) 2015 Sovan Pattanaik, Sudam Chandra Si, Sudhanshu Sekhar Rout, Anindya Bose , Siva Shankar Nayak