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

doi:10.1007/s13659-018-0193-7

Natural Products and Bioprospecting ›› 2019, Vol. 9 ›› Issue (1): 49-60.DOI: 10.1007/s13659-018-0193-7

• ORIGINAL ARTICLES • Previous Articles Next Articles

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

Received:2018-10-15 Online:2019-01-28 Published:2019-02-24
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.

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

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.

Abstract

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

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

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]. Natural Products and Bioprospecting, 2019, 9(1): 49-60.

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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

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