Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials
Malaria parasites are currently gaining drug-resistance rapidly, across countries and continents. Hence, the discovery and development of novel chemical scaffolds, with superior antimalarial activity remain an important priority, for the developing world. Our report describes the development, charac...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/81894 http://hdl.handle.net/10220/39739 |
| _version_ | 1824453722675085312 |
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| author | Anusha, Sebastian Sinha, Ameya Babu Rajeev, C. P. Chu, Trang T. T. Mathai, Jessin Huang, Ximei Fuchs, Julian E. Shivananju, NanjundaSwamy Bender, Andreas Preiser, Peter Rainer Rangappa, Kanchugarakoppal S. Basappa Chandramohanadas, Rajesh |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Anusha, Sebastian Sinha, Ameya Babu Rajeev, C. P. Chu, Trang T. T. Mathai, Jessin Huang, Ximei Fuchs, Julian E. Shivananju, NanjundaSwamy Bender, Andreas Preiser, Peter Rainer Rangappa, Kanchugarakoppal S. Basappa Chandramohanadas, Rajesh |
| author_sort | Anusha, Sebastian |
| collection | NTU |
| description | Malaria parasites are currently gaining drug-resistance rapidly, across countries and continents. Hence, the discovery and development of novel chemical scaffolds, with superior antimalarial activity remain an important priority, for the developing world. Our report describes the development, characterization and evaluation of novel bepotastine-based sulphonamide antimalarials inhibiting asexual stage development of Plasmodium falciparum parasites in vitro. The screening results showed potent inhibitory activity of a number of novel sulphonamides against P. falciparum at low micromolar concentrations, in particular in late-stage parasite development. Based on computational studies we hypothesize N-myristoyltransferase as the target of the compounds developed here. Our results demonstrate the value of novel bepotastine-based sulphonamide compounds for targeting the asexual developmental stages of P. falciparum. |
| first_indexed | 2025-02-19T03:10:56Z |
| format | Journal Article |
| id | ntu-10356/81894 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:10:56Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/818942023-02-28T16:59:12Z Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials Anusha, Sebastian Sinha, Ameya Babu Rajeev, C. P. Chu, Trang T. T. Mathai, Jessin Huang, Ximei Fuchs, Julian E. Shivananju, NanjundaSwamy Bender, Andreas Preiser, Peter Rainer Rangappa, Kanchugarakoppal S. Basappa Chandramohanadas, Rajesh School of Biological Sciences Drug discovery Giemsa-staining Microscopy Flow cytometry Anti-malarials Plasmodium falciparum In-vitro screening Malaria parasites are currently gaining drug-resistance rapidly, across countries and continents. Hence, the discovery and development of novel chemical scaffolds, with superior antimalarial activity remain an important priority, for the developing world. Our report describes the development, characterization and evaluation of novel bepotastine-based sulphonamide antimalarials inhibiting asexual stage development of Plasmodium falciparum parasites in vitro. The screening results showed potent inhibitory activity of a number of novel sulphonamides against P. falciparum at low micromolar concentrations, in particular in late-stage parasite development. Based on computational studies we hypothesize N-myristoyltransferase as the target of the compounds developed here. Our results demonstrate the value of novel bepotastine-based sulphonamide compounds for targeting the asexual developmental stages of P. falciparum. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) Accepted version 2016-01-21T04:22:12Z 2019-12-06T14:42:32Z 2016-01-21T04:22:12Z 2019-12-06T14:42:32Z 2015 Journal Article Anusha, S., Sinha, A., Babu Rajeev, C. P., Chu, T. T. T., Mathai, J., Huang, X., et al.. (2015). Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials. Org. Biomol. Chem., 13(43), 10681-10690. 1477-0520 https://hdl.handle.net/10356/81894 http://hdl.handle.net/10220/39739 10.1039/C5OB01479D en Organic & Biomolecular Chemistry © 2015 The Royal Society of Chemistry. This is the author created version of a work that has been peer reviewed and accepted for publication by Organic & Biomolecular Chemistry, The Royal Society of Chemistry. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1039/C5OB01479D]. 23 p. application/pdf |
| spellingShingle | Drug discovery Giemsa-staining Microscopy Flow cytometry Anti-malarials Plasmodium falciparum In-vitro screening Anusha, Sebastian Sinha, Ameya Babu Rajeev, C. P. Chu, Trang T. T. Mathai, Jessin Huang, Ximei Fuchs, Julian E. Shivananju, NanjundaSwamy Bender, Andreas Preiser, Peter Rainer Rangappa, Kanchugarakoppal S. Basappa Chandramohanadas, Rajesh Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials |
| title | Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials |
| title_full | Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials |
| title_fullStr | Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials |
| title_full_unstemmed | Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials |
| title_short | Synthesis, characterization and in vitro evaluation of novel enantiomerically-pure sulphonamide antimalarials |
| title_sort | synthesis characterization and in vitro evaluation of novel enantiomerically pure sulphonamide antimalarials |
| topic | Drug discovery Giemsa-staining Microscopy Flow cytometry Anti-malarials Plasmodium falciparum In-vitro screening |
| url | https://hdl.handle.net/10356/81894 http://hdl.handle.net/10220/39739 |
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