Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens
The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. H...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2017
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| Subjects: | |
| Online Access: | http://eprints.um.edu.my/17797/1/Synthesis_and_biological.pdf |
| _version_ | 1825720993961738240 |
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| author | Hong, W. Li, J. Chang, Z. Tan, X. Yang, H. Ouyang, Y. Yang, Y. Kaur, S. Paterson, I.C. Ngeow, Y.F. Wang, H. |
| author_facet | Hong, W. Li, J. Chang, Z. Tan, X. Yang, H. Ouyang, Y. Yang, Y. Kaur, S. Paterson, I.C. Ngeow, Y.F. Wang, H. |
| author_sort | Hong, W. |
| collection | UM |
| description | The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Four of these strains showed additional activity against Gram-negative bacteria, including extended-spectrum beta-lactamase producing Enterobacteriaceae, imipenem-resistant Klebsiella pneumoniae and multidrug-resistant Acinetobacter baumanii, and against Mycobacterium tuberculosis H37Ra. These four compounds are candidates for developing into broad-spectrum anti-infective agents. |
| first_indexed | 2024-03-06T05:43:34Z |
| format | Article |
| id | um.eprints-17797 |
| institution | Universiti Malaya |
| language | English |
| last_indexed | 2024-03-06T05:43:34Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | um.eprints-177972017-09-12T08:23:32Z http://eprints.um.edu.my/17797/ Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens Hong, W. Li, J. Chang, Z. Tan, X. Yang, H. Ouyang, Y. Yang, Y. Kaur, S. Paterson, I.C. Ngeow, Y.F. Wang, H. RK Dentistry The emergence of drug resistance in bacterial pathogens is a growing clinical problem that poses difficult challenges in patient management. To exacerbate this problem, there is currently a serious lack of antibacterial agents that are designed to target extremely drug-resistant bacterial strains. Here we describe the design, synthesis and antibacterial testing of a series of 40 novel indole core derivatives, which are predicated by molecular modeling to be potential glycosyltransferase inhibitors. Twenty of these derivatives were found to show in vitro inhibition of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Four of these strains showed additional activity against Gram-negative bacteria, including extended-spectrum beta-lactamase producing Enterobacteriaceae, imipenem-resistant Klebsiella pneumoniae and multidrug-resistant Acinetobacter baumanii, and against Mycobacterium tuberculosis H37Ra. These four compounds are candidates for developing into broad-spectrum anti-infective agents. Nature Publishing Group 2017 Article PeerReviewed application/pdf en http://eprints.um.edu.my/17797/1/Synthesis_and_biological.pdf Hong, W. and Li, J. and Chang, Z. and Tan, X. and Yang, H. and Ouyang, Y. and Yang, Y. and Kaur, S. and Paterson, I.C. and Ngeow, Y.F. and Wang, H. (2017) Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens. Journal of Antibiotics, 70 (7). pp. 832-844. ISSN 0021-8820, DOI https://doi.org/10.1038/ja.2017.55 <https://doi.org/10.1038/ja.2017.55>. http://www.nature.com/ja/journal/v70/n7/full/ja201755a.html doi:10.1038/ja.2017.55 |
| spellingShingle | RK Dentistry Hong, W. Li, J. Chang, Z. Tan, X. Yang, H. Ouyang, Y. Yang, Y. Kaur, S. Paterson, I.C. Ngeow, Y.F. Wang, H. Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens |
| title | Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens |
| title_full | Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens |
| title_fullStr | Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens |
| title_full_unstemmed | Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens |
| title_short | Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens |
| title_sort | synthesis and biological evaluation of indole core based derivatives with potent antibacterial activity against resistant bacterial pathogens |
| topic | RK Dentistry |
| url | http://eprints.um.edu.my/17797/1/Synthesis_and_biological.pdf |
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