Inhibitory Activity of Bioactive Phloroglucinols from the Rhizomes of Dryopteris Crassirhizoma on Escherichia Coli β-Glucuronidase: Kinetic Analysis and Molecular Docking Studies

Overview

Journal Metabolites

Publisher MDPI

Date 2022 Oct 27

PMID 36295840

Authors

Nguyen Viet Phong

Yan Zhao

Byung Sun Min

Seo Young Yang

Jeong Ah Kim

Affiliations

Soon will be listed here.

Abstract

Phloroglucinols-one of the major secondary metabolites in -exhibit various pharmacological effects, such as antiviral, antioxidant, and antidiabetic activities. This study evaluated 30 phloroglucinols isolated from the rhizomes of for their inhibitory activity on -glucuronidase via in vitro assays. Among them, dimeric phloroglucinols - moderately inhibited -glucuronidase, and trimeric phloroglucinols - showed strong inhibitory effects, with IC values ranging from 5.6 to 8.0 μM. Enzyme kinetic analysis confirmed all six active compounds to be in a competitive mode of inhibition. Molecular docking simulations revealed the key binding interactions with the active site of -glucuronidase protein and the binding mechanisms of these active metabolites. Our results suggest that the rhizomes of and trimeric compounds - may serve as potential candidates for discovering and developing new -glucuronidase inhibitors.

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References

Kim J, Vinh L, Hur M, Koo S, Park W, Moon Y . Inhibitory Activity of 4--Benzoyl-3'--(OMethylsinapoyl) Sucrose from on -Glucuronidase. J Microbiol Biotechnol. 2021; 31(11):1576-1582. PMC: 9705844. DOI: 10.4014/jmb.2108.08004. View

Morris G, Huey R, Lindstrom W, Sanner M, Belew R, Goodsell D . AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J Comput Chem. 2009; 30(16):2785-91. PMC: 2760638. DOI: 10.1002/jcc.21256. View

Michikawa M, Ichinose H, Momma M, Biely P, Jongkees S, Yoshida M . Structural and biochemical characterization of glycoside hydrolase family 79 β-glucuronidase from Acidobacterium capsulatum. J Biol Chem. 2012; 287(17):14069-77. PMC: 3340155. DOI: 10.1074/jbc.M112.346288. View

Yuk H, Kim J, Sung Y, Kim D . Phloroglucinol Derivatives from as Potent Xanthine Oxidase Inhibitors. Molecules. 2021; 26(1). PMC: 7796287. DOI: 10.3390/molecules26010122. View

Yang Q, Gao L, Si J, Sun Y, Liu J, Cao L . Inhibition of porcine reproductive and respiratory syndrome virus replication by flavaspidic acid AB. Antiviral Res. 2012; 97(1):66-73. DOI: 10.1016/j.antiviral.2012.11.004. View

Lee S, Na M, An R, Min B, Lee H . Antioxidant activity of two phloroglucinol derivatives from Dryopteris crassirhizoma. Biol Pharm Bull. 2003; 26(9):1354-6. DOI: 10.1248/bpb.26.1354. View

Phong N, Thi Nguyet Anh D, Yeong Chae H, Yang S, Kwon M, Min B . Anti-inflammatory activity and cytotoxicity against ovarian cancer cell lines by amide alkaloids and piperic esters isolated from Piper longum fruits: In vitro assessments and molecular docking simulation. Bioorg Chem. 2022; 128:106072. DOI: 10.1016/j.bioorg.2022.106072. View

Sun C, Yan J, Yi J, Zhang X, Yu Z, Huo X . The study of inhibitory effect of natural flavonoids toward β-glucuronidase and interaction of flavonoids with β-glucuronidase. Int J Biol Macromol. 2019; 143:349-358. DOI: 10.1016/j.ijbiomac.2019.12.057. View

Wang J, Yan Y, Fu S, Peng B, Bao L, Zhang Y . Anti-Influenza Virus (H5N1) Activity Screening on the Phloroglucinols from Rhizomes of Dryopteris crassirhizoma. Molecules. 2017; 22(3). PMC: 6155227. DOI: 10.3390/molecules22030431. View

10.

Phong N, Oanh V, Yang S, Choi J, Min B, Kim J . PTP1B inhibition studies of biological active phloroglucinols from the rhizomes of Dryopteris crassirhizoma: Kinetic properties and molecular docking simulation. Int J Biol Macromol. 2021; 188:719-728. DOI: 10.1016/j.ijbiomac.2021.08.091. View

11.

Lee J, Miyashiro H, Nakamura N, Hattori M . Two new triterpenes from the Rhizome of Dryopteris crassirhizoma, and inhibitory activities of its constituents on human immunodeficiency virus-1 protease. Chem Pharm Bull (Tokyo). 2008; 56(5):711-4. DOI: 10.1248/cpb.56.711. View

12.

Kuntz I, Blaney J, Oatley S, LANGRIDGE R, Ferrin T . A geometric approach to macromolecule-ligand interactions. J Mol Biol. 1982; 161(2):269-88. DOI: 10.1016/0022-2836(82)90153-x. View

13.

Pusztaszeri M, Genta R, Cryer B . Drug-induced injury in the gastrointestinal tract: clinical and pathologic considerations. Nat Clin Pract Gastroenterol Hepatol. 2007; 4(8):442-53. DOI: 10.1038/ncpgasthep0896. View

14.

Roberts A, Wallace B, Venkatesh M, Mani S, Redinbo M . Molecular insights into microbial β-glucuronidase inhibition to abrogate CPT-11 toxicity. Mol Pharmacol. 2013; 84(2):208-17. PMC: 3716326. DOI: 10.1124/mol.113.085852. View

15.

Chang S, Bae J, Hong D, Choi K, Kim S, Her E . Dryopteris crassirhizoma has anti-cancer effects through both extrinsic and intrinsic apoptotic pathways and G0/G1 phase arrest in human prostate cancer cells. J Ethnopharmacol. 2010; 130(2):248-54. DOI: 10.1016/j.jep.2010.04.038. View

16.

Torres P, Sodero A, Jofily P, Silva-Jr F . Key Topics in Molecular Docking for Drug Design. Int J Mol Sci. 2019; 20(18). PMC: 6769580. DOI: 10.3390/ijms20184574. View

17.

Cong P, Tuan Anh H, Quang Trung N, Minh B, Duc N, Dan N . Isolation, structural elucidation and molecular docking studies against SARS-CoV-2 main protease of new stigmastane-type steroidal glucosides isolated from the whole plants of . Nat Prod Res. 2022; 37(14):2342-2350. DOI: 10.1080/14786419.2022.2042534. View

18.

Cantarel B, Coutinho P, Rancurel C, Bernard T, Lombard V, Henrissat B . The Carbohydrate-Active EnZymes database (CAZy): an expert resource for Glycogenomics. Nucleic Acids Res. 2008; 37(Database issue):D233-8. PMC: 2686590. DOI: 10.1093/nar/gkn663. View

19.

Wallace B, Wang H, Lane K, Scott J, Orans J, Koo J . Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010; 330(6005):831-5. PMC: 3110694. DOI: 10.1126/science.1191175. View

20.

Houba P, Boven E, Leenders R, Scheeren J, Pinedo H, Haisma H . Pronounced antitumor efficacy of doxorubicin when given as the prodrug DOX-GA3 in combination with a monoclonal antibody beta-glucuronidase conjugate. Int J Cancer. 2001; 91(4):550-4. DOI: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1075>3.0.co;2-l. View