Insights into the Design of Inhibitors of the Urease Enzyme - A Major Target for the Treatment of Helicobacter pylori Infections

Author(s): Ana Thereza Fiori-Duarte, Ricardo Pereira Rodrigues, Rodrigo Rezende Kitagawa, Daniel Fábio Kawano*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 23 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor


Expressed by a variety of plants, fungi and bacteria, the urease enzyme is directly associated with the virulence factor of many bacteria, including Helicobacter pylori, a gram-negative bacterium related to several gastrointestinal diseases and responsible for one of the most frequent bacterial infections throughout the world. The Helicobacter pylori Urease (HPU) is a nickel-dependent metalloenzyme expressed in response to the environmental stress caused by the acidic pH of the stomach. The enzyme promotes the increase of gastric pH through acid neutralization by the products of urea hydrolysis, then critically contributing to the colonization and pathogenesis of the microorganism. At the same time, standard treatments for Helicobacter pylori infections have limitations such as the increasing bacterial resistance to the antibiotics used in the clinical practice. As a strategy for the development of novel treatments, urease inhibitors have proved to be promising, with a wide range of chemical compounds, including natural, synthetic and semisynthetic products to be researched and potentially developed as new drugs. In this context, this review highlights the advances in the field of HPU inhibition, presenting and discussing the basis for the research of new molecules aiming at the identification of more efficient therapeutic entities.

Keywords: Helicobacter pylori, urease, drug discovery, peptic ulcer, gastritis, gastric adenocarcinoma.

Sanders, M.K.; Peura, D.A. Helicobacter pylori-Associated Diseases. Curr. Gastroenterol. Rep., 2002, 4(6), 448-454.
[] [PMID: 12441033]
Howden, C.W.; Chey, W.D.; Vakil, N.B. Clinical rationale for confirmation testing after treatment of Helicobacter pylori infection: implications of rising antibiotic resistance. Gastroenterol. Hepatol. (N. Y.), 2014, 10(7)(Suppl. 3), 1-19.
[PMID: 25892981]
World Health Organization (WHO) Report from the World Health Organization’s Third Product Development for Vaccines Advisory Committee (PDVAC) Meeting, Geneva, 8-10th June 2016., Available at:. immunization/research/meetings_workshops/PDVAC_ 2016_report.pdf (Accessed: January 31, 2019).
Wroblewski, L.E.; Peek, R.M., Jr Helicobacter pylori: Pathogenic enablers - toxic relationships in the stomach. Nat. Rev. Gastroenterol. Hepatol., 2016, 13(6), 317-318.
[] [PMID: 27147493]
Roesler, B.M.; Rabelo-Gonçalves, E.M.A.; Zeitune, J.M.R. Virulence factors of Helicobacter pylori: a review. Clin. Med. Insights Gastroenterol., 2014, 7, 9-17.
[] [PMID: 24833944]
Hunt, R.H.; Xiao, S.D.; Megraud, F.; Leon-Barua, R.; Bazzoli, F.; van der Merwe, S.; Vaz Coelho, L.G.; Fock, M.; Fedail, S.; Cohen, H.; Malfertheiner, P.; Vakil, N.; Hamid, S.; Goh, K.L.; Wong, B.C.Y.; Krabshuis, J.; Le Mair, A. World Gastroenterology Organization. Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline. J. Gastrointestin. Liver Dis, 2011, 20(3), 299-304.
[PMID: 21961099]
Garza-González, E.; Perez-Perez, G.I.; Maldonado-Garza, H.J.; Bosques-Padilla, F.J. A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication. World J. Gastroenterol., 2014, 20(6), 1438-1449.
[] [PMID: 24587620]
Chey, W.D.; Leontiadis, G.I.; Howden, C.W.; Moss, S.F. ACG clinical guideline: treatment of Helicobacter pylori infection. Am. J. Gastroenterol., 2017, 112(2), 212-239.
[] [PMID: 28071659]
Safavi, M.; Sabourian, R.; Foroumadi, A. Treatment of Helicobacter pylori infection: Current and future insights. World J. Clin. Cases, 2016, 4(1), 5-19.
[] [PMID: 26798626]
Malfertheiner, P.; Megraud, F.; O’Morain, C.A.; Gisbert, J.P.; Kuipers, E.J.; Axon, A.T.; Bazzoli, F.; Gasbarrini, A.; Atherton, J.; Graham, D.Y.; Hunt, R.; Moayyedi, P.; Rokkas, T.; Rugge, M.; Selgrad, M.; Suerbaum, S.; Sugano, K.; El-Omar, E.M. European helicobacter and microbiota study group and consensus panel. Management of Helicobacter pylori infection- the Maastricht V/florence consensus report. Gut, 2017, 66(1), 6-30.
[] [PMID: 27707777]
World Health Organization (WHO). WHO publishes list of bacteria for which new antibiotics are urgently needed,, 2017.Available at:. news/releases/2017/bac teria-antibiotics-needed/en/
Sumner, J.B. The isolation and crystallization of the enzyme urease. Preliminary paper. J. Biol. Chem., 1926, 69, 435-441.
Mora, D.; Arioli, S. Microbial urease in health and disease. PLoS Pathog., 2014, 10(12)e1004472
[] [PMID: 25501953]
Kosikowska, P.; Berlicki, Ł. Urease inhibitors as potential drugs for gastric and urinary tract infections: a patent review. Expert Opin. Ther. Pat., 2011, 21(6), 945-957.
[] [PMID: 21457123]
Balasubramanian, A.; Ponnuraj, K. Purification, crystallization and preliminary X-ray analysis of urease from pigeon pea (Cajanus cajan). Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 2008, 64(Pt 7), 662-664.
[] [PMID: 18607103]
Dixon, N.E.; Gazzola, T.C.; blakeley, R.L.; Zermer, B. Letter: Jack bean urease (EC A metalloenzyme. A simple biological role for nickel? J. Am. Chem. Soc., 1975, 97(14), 4131-4133.
[] [PMID: 1159216]
Balasubramanian, A.; Ponnuraj, K. Crystal structure of the first plant urease from jack bean: 83 years of journey from its first crystal to molecular structure. J. Mol. Biol., 2010, 400(3), 274-283.
[] [PMID: 20471401]
Phadnis, S.H.; Parlow, M.H.; Levy, M.; Ilver, D.; Caulkins, C.M.; Connors, J.B.; Dunn, B.E. Surface localization of Helicobacter pylori urease and a heat shock protein homolog requires bacterial autolysis. Infect. Immun., 1996, 64(3), 905-912.
[] [PMID: 8641799]
Hassan, S.T.; Šudomová, M. The development of urease inhibitors: what opportunities exist for better treatment of Helicobacter pylori infection in children? Children (Basel), 2017, 4(1), 1-5.
[] [PMID: 28054971]
Scott, D.R.; Marcus, E.A.; Weeks, D.L.; Sachs, G. Mechanisms of acid resistance due to the urease system of Helicobacter pylori. Gastroenterology, 2002, 123(1), 187-195.
[] [PMID: 12105847]
Patrick, G. An introduction to medicinal chemistry, 6th ed; Oxford University Press, 2017.
Gordon, D. A pH-sensitive channel regulates urea access to Helicobacter pylori urease. Gastroenterology, 2000, 118(2), 249-250.
[] [PMID: 10691368]
Weeks, D.L.; Eskandari, S.; Scott, D.R.; Sachs, G. A H+-gated urea channel: the link between Helicobacter pylori urease and gastric colonization. Science, 2000, 287(5452), 482-485.
[] [PMID: 10642549]
Amieva, M.; Peek, R.M., Jr Pathobiology of Helicobacter pylori-induced gastric cancer. Gastroenterology, 2016, 150(1), 64-78.
[] [PMID: 26385073]
Mendz, G.L.; Holmes, E.M.; Ferrero, R.L. In situ characterization of Helicobacter pylori arginase. Biochim. Biophys. Acta, 1998, 1388(2), 465-477.
[] [PMID: 9858781]
Gobert, A.P.; McGee, D.J.; Akhtar, M.; Mendz, G.L.; Newton, J.C.; Cheng, Y.; Mobley, H.L.T.; Wilson, K.T. Helicobacter pylori arginase inhibits nitric oxide production by eukaryotic cells: a strategy for bacterial survival. Proc. Natl. Acad. Sci. USA, 2001, 98(24), 13844-13849.
[] [PMID: 11717441]
Gobert, A.P.; Wilson, K.T. The immune battle against Helicobacter pylori infection: no offense. Trends Microbiol., 2016, 24(5), 366-376.
[] [PMID: 26916789]
Malfertheiner, P.; Link, A.; Selgrad, M. Helicobacter pylori: perspectives and time trends. Nat. Rev. Gastroenterol. Hepatol., 2014, 11(10), 628-638.
[] [PMID: 25001975]
Foegeding, N.J.; Caston, R.R.; McClain, M.S.; Ohi, M.D.; Cover, T.L. An overview of Helicobacter pylori VacA toxin biology. Toxins (Basel), 2016, 8(6), 1-21.
[] [PMID: 27271669]
Cover, T.L.; Blaser, M.J. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J. Biol. Chem., 1992, 267(15), 10570-10575.
[PMID: 1587837]
Lima, V.P.; Rabenhorst, S.H.B. Genes associados à virulência de Helicobacter pylori. Rev. Bras. Cancerol., 2009, 55(4), 389-396.
Peter, J. Causes of failure of eradication of Helicobacter pylori antibiotic resistance is the major cause, and susceptibility testing may help. BMJ, 2002, 325(7354), 3-4.
[] [PMID: 12098709]
Odenbreit, S.; Püls, J.; Sedlmaier, B.; Gerland, E.; Fischer, W.; Haas, R. Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science, 2000, 287(5457), 1497-1500.
[] [PMID: 10688800]
Oleastro, M.; Ménard, A. The role of Helicobacter pylori outer membrane proteins in adherence and pathogenesis. Biology (Basel), 2013, 2(3), 1110-1134.
[] [PMID: 24833057]
Mobley, H.L.; Island, M.D.; Hausinger, R.P. Molecular biology of microbial ureases. Microbiol. Rev., 1995, 59(3), 451-480.
[] [PMID: 7565414]
Scott, D.R.; Marcus, E.A.; Weeks, D.L.; Lee, A.; Melchers, K.; Sachs, G. Expression of the Helicobacter pylori ureI gene is required for acidic pH activation of cytoplasmic urease. Infect. Immun., 2000, 68(2), 470-477.
[] [PMID: 10639406]
Skouloubris, S.; Thiberge, J.M.; Labigne, A.; De Reuse, H. The Helicobacter pylori UreI protein is not involved in urease activity but is essential for bacterial survival in vivo. Infect. Immun., 1998, 66(9), 4517-4521.
[] [PMID: 9712811]
Scott, D.R.; Marcus, E.A.; Wen, Y.; Oh, J.; Sachs, G. Gene expression in vivo shows that Helicobacter pylori colonizes an acidic niche on the gastric surface. Proc. Natl. Acad. Sci. USA, 2007, 104(17), 7235-7240.
[] [PMID: 17438279]
Ha, N.C.; Oh, S.T.; Sung, J.Y.; Cha, K.A.; Lee, M.H.; Oh, B.H. Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat. Struct. Biol., 2001, 8(6), 505-509.
[] [PMID: 11373617]
Mobley, H.L.T. Helicobacter pylori: physiology and genetics, Urease. Am. Soc. Microbiol.,, 2001, 179-191.
[] [PMID: 21290719]
Minkara, M.S.; Ucisik, M.N.; Weaver, M.N.; Merz, K.M., Jr Molecular dynamics study of Helicobacter pylori urease. J. Chem. Theory Comput., 2014, 10(5), 1852-1862.
[] [PMID: 24839409]
Pinkse, M.W.H.; Maier, C.S.; Kim, J.I.; Oh, B.H.; Heck, A.J.R. Macromolecular assembly of Helicobacter pylori urease investigated by mass spectrometry. J. Mass Spectrom., 2003, 38(3), 315-320.
[] [PMID: 12644993]
Ha, N.C.; Oh, S.T.; Oh, B.H. 1E97: Crystal structure of Helicobacter pylori urease,, 2001.Available at:.
Habala, L.; Devínsky, F.; Egger, A.E. Review: metal complexes as urease inhibitors. J. Coord. Chem., 2018, 71, 907-940.
Krajewska, B.; Ureases, I. Functional, catalytic and kinetic properties: a review. J. Mol. Catal., B Enzym., 2009, 59(1-3), 9-21.
Amtul, Z.; Rahman, A.U.; Siddiqui, R.A.; Choudhary, M.I. Chemistry and mechanism of urease inhibition. Curr. Med. Chem., 2002, 9(14), 1323-1348.
[] [PMID: 12132990]
Debraekeleer, A.; Remaut, H. Future perspective for potential Helicobacter pylori eradication therapies. Future Microbiol., 2018, 13, 671-687.
[] [PMID: 29798689]
Shah, M.R.; Soomro, Z.H. Urease inhibition In. Enzyme Inhibition and Bioapplications, 2012, 303-314.
Upadhyay, L.S.B. Urease inhibitors: a review. Indian J. Biotechnol., 2012, 11(4), 381-388.
Sheng, G.H.; Zhou, Q.C.; Hu, X.M.; Wang, C.F.; Chen, X.F.; Xue, D.; Yan, K.; Ding, S.S.; Wang, J.; Du, Z.Y.; Liu, Z.H.; Zhang, C.Y.; Zhu, H.L. Synthesis, structure, urease inhibitory, and cytotoxic activities of two complexes with protocatechuic acid derivative and phenanthroline. J. Coord. Chem., 2015, 68(9), 1571-1582.
Shaw, W.H.R. The inhibition of urease by various metal ions. J. Am. Chem. Soc., 1954, 76(8), 2160-2163.
Shaw, W.H.R.; Raval, D.N. The inhibition of urease by metal ions at pH 8.9. J. Am. Chem. Soc., 1961, 83(15), 3184-3187.
Ambrose, J.F.; Kistiakowsky, G.B.; Kridl, A.G. Inhibition of urease by silver ions. J. Am. Chem. Soc., 1951, 73(3), 1232-1236.
Pan, L.; Wang, C.; Yan, K.; Zhao, K.; Sheng, G.; Zhu, H.; Zhao, X.; Qu, D.; Niu, F.; You, Z. Synthesis, structures and Helicobacter pylori urease inhibitory activity of copper(II) complexes with tridentate aroylhydrazone ligands. J. Inorg. Biochem., 2016, 159, 22-28.
[] [PMID: 26908284]
You, Z.; Liu, M.; Wang, C.; Sheng, G.; Zhao, X.; Qu, D.; Niu, F. Inhibition studies of Helicobacter pylori urease with Schiff base copper(II) complexes. RSC Advances, 2016, 6(20), 16679-16690.
de Fátima, Â.; Pereira, C.P.; Olímpio, C.R.S.D.G.; de Freitas Oliveira, B.G.; Franco, L.L.; da Silva, P.H.C. Schiff bases and their metal complexes as urease inhibitors - A brief review. J. Adv. Res., 2018, 13, 113-126.
[] [PMID: 30094086]
You, Z.L.; Lu, Y.; Zhang, N.; Ding, B.W.; Sun, H.; Hou, P.; Wang, C. Preparation and structural characterization of hetero- dinuclear Schiff base copper(II)-zinc(II) complexes and their inhibition studies on Helicobacter pylori urease. Polyhedron, 2011, 30(13), 2186-2194.
Sangeeta, S.; Ahmad, K.; Noorussabah, N.; Bharti, S.; Mishra, M.K.; Sharma, S.R.; Choudhary, M. Synthesis, crystal structures, molecular docking and urease inhibition studies of Ni(II) and Cu(II) Schiff base complexes. J. Mol. Struct., 2018, 1156(15), 1-11.
Kobashi, K.; Hase, J.; Uehara, K. Specific inhibition of urease by hydroxamic acids. Biochim. Biophys. Acta, 1962, 65, 380-383.
[] [PMID: 14033904]
Odake, S.; Morikawa, T.; Tsuchiya, M.; Imamura, L.; Kobashi, K. Inhibition of Helicobacter pylori urease activity by hydroxamic acid derivatives. Biol. Pharm. Bull., 1994, 17(10), 1329-1332.
[] [PMID: 7874052]
Xiao, Z.P.; Peng, Z.Y.; Dong, J.J.; Deng, R.C.; Wang, X.D.; Ouyang, H.; Yang, P.; He, J.; Wang, Y.F.; Zhu, M.; Peng, X.C.; Peng, W.X.; Zhu, H.L. Synthesis, molecular docking and kinetic properties of β-hydroxy-β-phenylpropionyl-hydroxamic acids as Helicobacter pylori urease inhibitors. Eur. J. Med. Chem., 2013, 68, 212-221.
[] [PMID: 23974021]
Kumar, S.; Kayastha, A.M. Acetohydroxamic acid - a competitive inhibitor of urease from soybean “Glycine max”. J. Proteins Proteomics, 2010, 1(1), 3-8.
Zhou, J.T.; Li, C.L.; Tan, L.H.; Xu, Y.F.; Liu, Y.H.; Mo, Z.Z.; Dou, Y.X.; Su, R.; Su, Z.R.; Huang, P.; Xie, J.H. Inhibition of Helicobacter pylori and its associated urease by palmatine: investigation on the potential mechanism. PLoS One, 2017, 12(1)e0168944
[] [PMID: 28045966]
Kobashi, K.; Kumaki, K.; Hase, J.I. Effect of acyl residues of hydroxamic acids on urease inhibition. Biochim. Biophys. Acta, 1971, 227(2), 429-441.
[] [PMID: 5550827]
Ni, W.W.; Liu, Q.; Ren, S.Z.; Li, W.Y.; Yi, L.L.; Jing, H.; Sheng, L.X.; Wan, Q.; Zhong, P.F.; Fang, H.L.; Ouyang, H.; Xiao, Z.P.; Zhu, H.L. The synthesis and evaluation of phenoxyacylhydroxamic acids as potential agents for Helicobacter pylori infections. Bioorg. Med. Chem., 2018, 26(14), 4145-4152.
[] [PMID: 29983280]
Pope, A.J.; Toseland, C.D.; Rushant, B.; Richardson, S.; McVey, M.; Hills, J. Effect of potent urease inhibitor, fluorofamide, on Helicobacter sp. in vivo and in vitro. Dig. Dis. Sci., 1998, 43(1), 109-119.
[] [PMID: 9508511]
Faraci, W.S.; Yang, B.V.; O’Rourke, D.; Spencer, R.W. Inhibition of Helicobacter pylori urease by phenyl phosphorodiamidates: mechanism of action. Bioorg. Med. Chem., 1995, 3(5), 605-610.
[] [PMID: 7648208]
Follmer, C. Ureases as a target for the treatment of gastric and urinary infections. J. Clin. Pathol., 2010, 63(5), 424-430.
[] [PMID: 20418234]
Oliveira, F.M.; Barbosa, L.C.A.; Demuner, A.J.; Maltha, C.R.A.; Pereira, S.R.; Horta, L.P.; Modolo, L.V. Synthesis, molecular properties and DFT studies of new phosphoramidates as potential urease inhibitors. Med. Chem. Res., 2014, 23, 5174-5187.
Kafarski, P.; Talma, M. Recent advances in design of new urease inhibitors: A review. J. Adv. Res., 2018, 13, 101-112.
[] [PMID: 30094085]
Rauf, A.; Shahzad, S.; Bajda, M.; Yar, M.; Ahmed, F.; Hussain, N.; Akhtar, M.N.; Khan, A.; Jończyk, J. Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies. Bioorg. Med. Chem., 2015, 23(17), 6049-6058.
[] [PMID: 26081763]
Barakat, A.; Al-Majid, A.M.; Lotfy, G.; Arshad, F.; Yousuf, S.; Choudhary, M.I.; Ashraf, S.; Ul-Haq, Z. Synthesis and dynamics studies of barbituric acid derivatives as urease inhibitors. Chem. Cent. J., 2015, 9, 63.
[] [PMID: 26583043]
Sivapriya, K.; Suguna, P.; Banerjee, A.; Saravanan, V.; Rao, D.N.; Chandrasekaran, S. Facile one-pot synthesis of thio and selenourea derivatives: a new class of potent urease inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(22), 6387-6391.
[] [PMID: 17889535]
Tago, K.; Minami, E.; Masuda, K.; Akiyama, T.; Kogen, H. Synthesis of plaunotol derivatives and their antibacterial activities against Helicobacter pylori. Bioorg. Med. Chem., 2001, 9(7), 1781-1791.
[] [PMID: 11425580]
Kogen, H.; Tago, K.; Arai, M.; Minami, E.; Masuda, K.; Akiyama, T. A highly stereoselective synthesis of plaunotol and its thiourea derivatives as potent antibacterial agents against Helicobacter pylori. Bioorg. Med. Chem. Lett., 1999, 9(10), 1347-1350.
[] [PMID: 10360733]
Uesato, S.; Hashimoto, Y.; Nishino, M.; Nagaoka, Y.; Kuwajima, H. N-substituted hydroxyureas as urease inhibitors. Chem. Pharm. Bull. (Tokyo), 2002, 50(9), 1280-1282.
[] [PMID: 12237554]
Saeed, A.; Ur-Rehman, S.; Channar, P.A.; Larik, F.A.; Abbas, Q.; Hassan, M.; Raza, H.; Seo, S.Y. Jack bean urease inhibitors, and antioxidant activity based on palmitic acid derived 1-acyl-3- arylthioureas: synthesis, kinetic mechanism and molecular docking studies. Drug Res. (Stuttg.), 2017, 67(10), 596-605.
[] [PMID: 28672409]
Rauf, M.K.; Yaseen, S.; Badshah, A.; Zaib, S.; Arshad, R.; Imtiaz-Ud-Din, ; Tahir, M.N.; Iqbal, J. Synthesis, characterization and urease inhibition, in vitro anticancer and antileishmanial studies of Ni(II) complexes with N,N,N′-trisubstituted thioureas. J. Biol. Inorg. Chem., 2015, 20(3), 541-554.
[] [PMID: 25604966]
Modolo, L.V.; de Souza, A.X.; Horta, L.P.; Araujo, D.P.; de Fátima, Â. An overview on the potential of natural products as ureases inhibitors: A review. J. Adv. Res., 2015, 6(1), 35-44.
[] [PMID: 25685542]
Xiao, Z.P.; Peng, Z.Y.; Dong, J.J.; He, J.; Ouyang, H.; Feng, Y.T.; Lu, C.L.; Lin, W.Q.; Wang, J.X.; Xiang, Y.P.; Zhu, H.L. Synthesis, structure-activity relationship analysis and kinetics study of reductive derivatives of flavonoids as Helicobacter pylori urease inhibitors. Eur. J. Med. Chem., 2013, 63, 685-695.
[] [PMID: 23567958]
Ichikawa, S. Function-oriented synthesis: how to design simplified analogues of antibacterial nucleoside natural products? Chem. Rec., 2016, 16(3), 1106-1115.
[] [PMID: 27027613]
Tabak, M.; Armon, R.; Neeman, I. Cinnamon extracts’ inhibitory effect on Helicobacter pylori. J. Ethnopharmacol., 1999, 67(3), 269-277.
[] [PMID: 10617061]
Amin, M.; Anwar, F.; Naz, F.; Mehmood, T.; Saari, N. Anti-Helicobacter pylori and urease inhibition activities of some traditional medicinal plants. Molecules, 2013, 18(2), 2135-2149.
[] [PMID: 23434867]
Biglar, M.; Soltani, K.; Nabati, F.; Bazl, R.; Mojab, F.; Amanlou, M. A preliminary investigation of the jack-bean urease inhibition by randomly selected traditionally used herbal medicine. Iran. J. Pharm. Res., 2012, 11(3), 831-837.
[PMID: 24250509]
Xiao, Z.P.; Peng, Z.Y.; Peng, M.J.; Yan, W.B.; Ouyang, Y.Z.; Zhu, H.L. Flavonoids health benefits and their molecular mechanism. Mini Rev. Med. Chem., 2011, 11(2), 169-177.
[] [PMID: 21222576]
Xiao, Z.P.; Wang, X.D.; Peng, Z.Y.; Huang, S.; Yang, P.; Li, Q.S.; Zhou, L.H.; Hu, X.J.; Wu, L.J.; Zhou, Y.; Zhu, H.L. Molecular docking, kinetics study, and structure-activity relationship analysis of quercetin and its analogous as Helicobacter pylori urease inhibitors. J. Agric. Food Chem., 2012, 60(42), 10572-10577.
[] [PMID: 23067328]
Li, C.; Lin, G.; Zuo, Z. Pharmacological effects and pharmacokinetics properties of Radix Scutellariae and its bioactive flavones. Biopharm. Drug Dispos., 2011, 32(8), 427-445.
[] [PMID: 21928297]
Lee, B.W.; Park, I.H.; Yim, D.; Choi, S.S. Comprehensive evaluation of the anti- Helicobacter pylori activity of Scutellariae radix. Nat. Prod. Sci., 2017, 23(1), 46.
Tan, L.; Li, C.; Chen, H.; Mo, Z.; Zhou, J.; Liu, Y.; Ma, Z.; Xu, Y.; Yang, X.; Xie, J.; Su, Z. Epiberberine, a natural protoberberine alkaloid, inhibits urease of Helicobacter pylori and jack bean: Susceptibility and mechanism. Eur. J. Pharm. Sci., 2017, 110, 77-86.
[] [PMID: 28167234]
Lage, T.C.A.; Maciel, T.M.S.; Mota, Y.C.C.; Sisto, F.; Sabino, J.R.; Santos, J.C.C.; Figueiredo, I.M.; Masia, C.; De Fátima, Â.; Fernandes, S.A.; Modolo, L.V. In vitro inhibition of Helicobacter pylori and interaction studies of lichen natural products with jack bean urease. New J. Chem., 2018, 42(7), 5356-5366.
Nostro, A.; Cellini, L.; Di Bartolomeo, S.; Di Campli, E.; Grande, R.; Cannatelli, M.A.; Marzio, L.; Alonzo, V. Antibacterial effect of plant extracts against Helicobacter pylori. Phytother. Res., 2005, 19(3), 198-202.
[] [PMID: 15934015]
O’Gara, E.A.; Hill, D.J.; Maslin, D.J. Activities of garlic oil, garlic powder, and their diallyl constituents against Helicobacter pylori. Appl. Environ. Microbiol., 2000, 66(5), 2269-2273.
[] [PMID: 10788416]
Cellini, L.; Di Campli, E.; Masulli, M.; Di Bartolomeo, S.; Allocati, N. Inhibition of Helicobacter pylori by garlic extract (Allium sativum). FEMS Immunol. Med. Microbiol., 1996, 13(4), 273-277.
[] [PMID: 8739190]
Fahey, J.W.; Haristoy, X.; Dolan, P.M.; Kensler, T.W.; Scholtus, I.; Stephenson, K.K.; Talalay, P.; Lozniewski, A. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc. Natl. Acad. Sci. USA, 2002, 99(11), 7610-7615.
[] [PMID: 12032331]
Yanaka, A.; Fahey, J.W.; Fukumoto, A.; Nakayama, M.; Inoue, S.; Zhang, S.; Tauchi, M.; Suzuki, H.; Hyodo, I.; Yamamoto, M. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev. Res. (Phila.), 2009, 2(4), 353-360.
[] [PMID: 19349290]
U.S. Food and Drug Administration (FDA). FDA Approved Drug Products 2020.Available at:. http://www.accessdata.
Macegoniuk, K.; Grela, E.; Palus, J.; Rudzińska-Szostak, E.; Grabowiecka, A.; Biernat, M.; Berlicki, Ł. 1,2- Benzisoselenazol-3(2 H)-one derivatives as a new class of bacterial urease inhibitors. J. Med. Chem., 2016, 59(17), 8125-8133.
[] [PMID: 27524377]
Parnham, M.J.; Sies, H. The early research and development of ebselen. Biochem. Pharmacol., 2013, 86(9), 1248-1253.
[] [PMID: 24012716]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 01 July, 2020
Page: [3967 - 3982]
Pages: 16
DOI: 10.2174/0929867326666190301143549
Price: $65

Article Metrics

PDF: 44
PRC: 1