Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring β-Amyrenone

doi:10.1007/s13659-018-0193-7

应用天然产物 ›› 2019, Vol. 9 ›› Issue (1): 49-60.DOI: 10.1007/s13659-018-0193-7

Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring β-Amyrenone

Jean J. K. Bankeu^1,2, Hira Sattar², Yannick S. F. Fongang^2,3, Syeda W. Muhammadi², Conrad V. Simoben⁴, Fidele Ntie-Kang^4,5, Guy R. T. Feuya⁶, Marthe A. T. Tchuenmogne⁷, Mehreen Lateef⁸, Bruno N. Lenta⁹, Muhammad S. Ali², Augustin S. Ngouela⁷

1 Department of Chemistry, Faculty of Science, The University of Bamenda, P. O. Box 39, Bambili, Cameroon;
2 International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;
3 Department of Chemistry, Higher Teacher Training College, University of Maroua, P. O. Box 55, Maroua, Cameroon;
4 Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle(Saale), Germany;
5 Department of Chemistry, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon;
6 Department of Chemistry, Faculty of Science, Scientific and Technical University of Masuku, Box 943, Franceville, Gabon;
7 Department of Chemistry, Faculty of Science, University of Yaoundé I, P. O. Box 812, Yaoundé, Cameroon;
8 Multi-Disciplinary Research Laboratory(MDRL), Bahria University Medical and Dental College, Bahria University, Karachi, Pakistan;
9 Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon

收稿日期:2018-10-15 出版日期:2019-02-24 发布日期:2019-01-28
通讯作者: Jean J. K. Bankeu, Fidele Ntie-Kang, Bruno N. Lenta
基金资助:
BKJJ acknowledges The World Academy of Sciences (TWAS) and the International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan for their financial and technical support through the ICCBS-TWAS Postdoctoral Fellowship number 3240280476.

Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring β-Amyrenone

1 Department of Chemistry, Faculty of Science, The University of Bamenda, P. O. Box 39, Bambili, Cameroon;
2 International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan;
3 Department of Chemistry, Higher Teacher Training College, University of Maroua, P. O. Box 55, Maroua, Cameroon;
4 Department of Pharmaceutical Chemistry, Martin-Luther University of Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle(Saale), Germany;
5 Department of Chemistry, Faculty of Science, University of Buea, P. O. Box 63, Buea, Cameroon;
6 Department of Chemistry, Faculty of Science, Scientific and Technical University of Masuku, Box 943, Franceville, Gabon;
7 Department of Chemistry, Faculty of Science, University of Yaoundé I, P. O. Box 812, Yaoundé, Cameroon;
8 Multi-Disciplinary Research Laboratory(MDRL), Bahria University Medical and Dental College, Bahria University, Karachi, Pakistan;
9 Department of Chemistry, Higher Teacher Training College, University of Yaoundé I, P. O. Box 47, Yaoundé, Cameroon

Received:2018-10-15 Online:2019-02-24 Published:2019-01-28
Contact: Jean J. K. Bankeu, Fidele Ntie-Kang, Bruno N. Lenta
Supported by:
BKJJ acknowledges The World Academy of Sciences (TWAS) and the International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Pakistan for their financial and technical support through the ICCBS-TWAS Postdoctoral Fellowship number 3240280476.

摘要/Abstract

摘要： Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2-4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC₅₀ values ranging from 14.5 to 24.6 lM, with compound (1) being the most potent as compared to the positive control thiourea (IC₅₀=21.6 μM). Amongst the synthetic derivatives, compound 4 was the most potent (IC_50-=17.9 μM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2-4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.

关键词: Helicobacter pylori, Urease inhibition, Docking, Olean-12-en-3-one derivatives

Abstract: Urease enzyme (UE) has been reported to be a potent virulence factor for Helicobacter pylori (HP) bacteria indicated to be responsible for various gastrointestinal diseases. Therefore, the spread of HP, currently regarded by the World Health Organization as a class 1 carcinogen, could be better controlled by targeting UE. It is in this line that we have synthesized three new derivatives (2-4) of the naturally occurring olean-12-en-3-one (1), which was previously isolated from the figs of Ficus vallis-choudae Delile (Moraceae). Among the synthesized compounds, 3 and 4 contain an indole moiety. Their structures were unambiguously assigned by spectroscopic and spectrometric techniques (1D-NMR, 2D-NMR and MS). The starting material and the synthesized compounds were screened for UE inhibition activity, and showed significant activities with IC₅₀ values ranging from 14.5 to 24.6 lM, with compound (1) being the most potent as compared to the positive control thiourea (IC₅₀=21.6 μM). Amongst the synthetic derivatives, compound 4 was the most potent (IC_50-=17.9 μM), while the others showed activities close to that of the control. In addition, molecular docking study of target compounds 2-4 was performed in an attempt to explore their binding mode for the design of more potent UE inhibitors.

Key words: Helicobacter pylori, Urease inhibition, Docking, Olean-12-en-3-one derivatives

Jean J. K. Bankeu, Hira Sattar, Yannick S. F. Fongang, Syeda W. Muhammadi, Conrad V. Simoben, Fidele Ntie-Kang, Guy R. T. Feuya, Marthe A. T. Tchuenmogne, Mehreen Lateef, Bruno N. Lenta, Muhammad S. Ali, Augustin S. Ngouela. Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring β-Amyrenone[J]. 应用天然产物, 2019, 9(1): 49-60.

参考文献

1. J.G. Kusters, A.H.M. van Vliet, E.J. Kuipers, Clin. Microbiol. Rev. 19, 449-490 (2006)
2. H.M. Malaty, Best Pract. Res. Clin. Gastroenterol. 21, 205-214 (2007)
3. K.A. Eaton, S. Krakowka, Infect. Immun. 62, 3604-3607 (1994)
4. R.J. Maier, C. Fu, J. Gilbert, F. Moshiri, J. Olson, A.G. Plaut, FEMS Microbiol. Lett. 141, 71-76 (1996)
5. J.W. Olson, R.J. Maier, Science 298, 1788-1790 (2002)
6. A.M. Sydor, H. Lebrette, R. Ariyakumaran, C. Cavazza, D.B. Zamble, J. Biol. Chem. 289, 3828-3841 (2014)
7. J.J.K. Bankeu, S. Madjouka, G.R.T. Feuya, Y.S.F. Fongang, S. Siddiqui, I. Ali, L. Mehreen, B.N. Lenta, S. Yousuf, D.T. Noungoué, A.S. Ngouela, M.S. Ali, Z. Naturforsch. C 73, 335-3344 (2018)
8. K.B. Wang, X. Hu, S.G. Li, X.Y. Li, D.H. Li, J. Bai, Y.H. Pei, Z.L. Li, H.M. Hu, Fitoterapia 125, 155-160 (2018)
9. J. Yang, J. Fu, X. Liu, Z.H. Jiang, G.Y. Zhu, Fitoterapia 124, 73-79 (2018)
10. G.J. Zhang, F. Hu, H. Jiang, L.M. Dai, H.B. Liao, N. Li, H.S. Wang, Y.M. Pan, D. Liang, Phytochemistry 145, 68-76 (2018)
11. E. Yesilada, I. Gurbuz, H. Shibata, J. Ethnopharmacol. 66, 289-293 (1999)
12. C.C. Huang, K.W. Tsai, T.J. Tsai, P.I. Hsu, Biomark. Res. 5, 23 (2017)
13. J.J.K. Bankeu, A. Dawé, M. Mbiantcha, G.R.T. Feuya, I. Ali, M.A.T. Tchouenmogne, L. Mehreen, B.N. Lenta, M.S. Ali, S. Ngouela, Trends Phytochem. Res. 1, 235-242 (2017)
14. S.K. Burley, H.M. Berman, C. Christie, J.M. Duarte, Z. Feng, J. Westbrook, J. Young, C. Zardecki, Protein Sci. 27, 316-330 (2018)
15. Chemical Computing Group Inc., Molecular Operating Environment (MOE), version 2016.08 (QC H3A 2R7, Montreal, Canada, 2016)
16. G.M. Sastry, M. Adzhigirey, T. Day, R. Annabhimoju, W. Sherman, Comput.-Aided Mol. Des. 27, 221-234 (2013)
17. Schrödinger Release 2017-2, Schrödinger Suite 2017-2 Protein Preparation Wizard; (Epik, Schrödinger, LLC, New York, 2017a)
18. J.L. Banks, H.S. Beard, Y. Cao, A.E. Cho, W. Damm, R. Farid, A.K. Felts, T.A. Halgren, D.T. Mainz, J.R. Maple, R. Murphy, D.M. Philipp, M.P. Repasky, L.Y. Zhang, B.J. Berne, R.A. Friesner, E. Gallicchio, R.M. Levy, J. Comput. Chem. 26, 1752-1780 (2005)
19. Schrödinger Release 2017-2, LigPrep, (Schrödinger, LLC, New York, 2017b)
20. Schrödinger Release 2017-2, Canvas, version 3.1.011, (Schrödinger, LLC, New York 2017c)
21. J.B. Baell, G.A. Holloway, J. Med. Chem. 53, 2719-2740 (2010)
22. Schrödinger Release 2017-2, ConfGen, (Schrödinger, LLC, New York, 2017d)
23. K.S. Watts, P. Dalal, R.B. Murphy, W. Sherman, R.A. Friesner, J.C. Shelley, J. Chem. Inf. Model. 50, 534-546 (2010)
24. R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis, P.S. Shenkin, J. Med. Chem. 47, 1739-1749 (2004)
25. T.A. Halgren, R.B. Murphy, R.A. Friesner, H.S. Beard, L.L. Frye, W.T. Pollard, J.L. Banks, J. Med. Chem. 47, 1750-1759 (2004)
26. Schrödinger Release 2017-2, Glide, (Schrödinger, LLC, New York, 2017e)
27. Y.H. Fong, H.C. Wong, C.P. Chuck, Y.W. Chen, H. Sun, K.B. Wong, J. Biol. Chem. 286, 43241-43249 (2011)
28. Y.H. Fong, H.C. Wong, M.H. Yuen, P.H. Lau, Y.W. Chen, K.B. Wong, PLoS Biol. 11, e1001678 (2013)

[1]	Orawan Jongsomjainuk, Jutatip Boonsombat, Sanit Thongnest, Hunsa Prawat, Paratchata Batsomboon, Sitthivut Charoensutthivarakul, Saroj Ruchisansakun, Kittipong Chainok, Jitnapa Sirirak, Chulabhorn Mahidol, Somsak Ruchirawat. Kaemtakols A–D, highly oxidized pimarane diterpenoids with potent anti-inflammatory activity from Kaempferia takensis[J]. 应用天然产物, 2023, 13(6): 55-55.
[2]	Mohammed A. Dahab, Mostafa M. Hegazy, Hatem S. Abbass. Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach[J]. 应用天然产物, 2020, 10(6): 453-462.
[3]	Rohan R. Narkhede, Ashwini V. Pise, Rameshwar S. Cheke, Sachin D. Shinde. Recognition of Natural Products as Potential Inhibitors of COVID-19 Main Protease (Mpro): In-Silico Evidences[J]. 应用天然产物, 2020, 10(5): 297-306.
[4]	Yinglan Pu, Hui Liu, Yeheng Zhou, Jiale Peng, Yaping Li, Penghua Li, Yingying Li, Xingyong Liu, Li Zhang. In silico Discovery of Novel FXa Inhibitors by Pharmacophore Modeling and Molecular Docking[J]. 应用天然产物, 2017, 7(3): 249-256.
[5]	Mehtab Parveen, Faheem Ahmad, Ali Mohammed Malla, Shaista Azaz, Mahboob Alam, Omer A. Basudan, Manuela Ramos Silva, Pedro S. Pereira Silva. Acetylcholinesterase and Cytotoxic Activity of Chemical Constituents of Clutia lanceolata Leaves and its Molecular Docking Study[J]. 应用天然产物, 2016, 6(6): 267-278.
[6]	Christian Bäcker, Malgorzata N. Drwal, Robert Preissner, Ulrike Lindequist. Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd[J]. 应用天然产物, 2016, 6(2): 141-147.
[7]	A. Anita Margret, T. Nargis Begum, S. Parthasarathy, S. Suvaithenamudhan. A Strategy to Employ Clitoria ternatea as a Prospective Brain Drug Confronting Monoamine Oxidase (MAO) Against Neurodegenerative Diseases and Depression[J]. 应用天然产物, 2015, 5(6): 293-306.
[8]	David Mary Rajathei, Jayakumar Preethi, Hemant K. Singh, Koilmani Emmanuvel Rajan. Molecular Docking of Bacosides with Tryptophan Hydroxylase: A Model to Understand the Bacosides Mechanism[J]. 应用天然产物, 2014, 4(4): 251-255.
[9]	Tomofumi Miyamoto, Tadayoshi Okimoto, Michihiko Kuwano. Chemical Composition of the Essential Oil of Mastic Gum and their Antibacterial Activity Against Drug-Resistant Helicobacter pylori[J]. 应用天然产物, 2014, 4(4): 227-231.

Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring β-Amyrenone

Synthesis, Urease Inhibition and Molecular Modelling Studies of Novel Derivatives of the Naturally Occurring β-Amyrenone

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 9

编辑推荐

Metrics

本文评价