Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum
Abstract Background Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12936-021-03632-2 |
| _version_ | 1818411399773159424 |
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| author | Akshaykumar Nayak Himani Saxena Chandramohan Bathula Tarkeshwar Kumar Souvik Bhattacharjee Subhabrata Sen Ashish Gupta |
| author_facet | Akshaykumar Nayak Himani Saxena Chandramohan Bathula Tarkeshwar Kumar Souvik Bhattacharjee Subhabrata Sen Ashish Gupta |
| author_sort | Akshaykumar Nayak |
| collection | DOAJ |
| description | Abstract Background Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment. Methods The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-β-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library. Results Among all the compounds screened, 1-aryltetrahydro-β-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds. Conclusion Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum. |
| first_indexed | 2024-12-14T10:30:48Z |
| format | Article |
| id | doaj.art-262f3d88b503414db572f6dd0ee77cbe |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-14T10:30:48Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-262f3d88b503414db572f6dd0ee77cbe2022-12-21T23:06:09ZengBMCMalaria Journal1475-28752021-02-012011810.1186/s12936-021-03632-2Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparumAkshaykumar Nayak0Himani Saxena1Chandramohan Bathula2Tarkeshwar Kumar3Souvik Bhattacharjee4Subhabrata Sen5Ashish Gupta6Epigenetics & Human Disease Laboratory, Department of Life Sciences, Shiv Nadar University, Uttar PradeshEpigenetics & Human Disease Laboratory, Department of Life Sciences, Shiv Nadar University, Uttar PradeshDepartment of Chemistry, Shiv Nadar University, Uttar PradeshSpecial Centre for Molecular Medicine, Jawaharlal Nehru UniversitySpecial Centre for Molecular Medicine, Jawaharlal Nehru UniversityDepartment of Chemistry, Shiv Nadar University, Uttar PradeshEpigenetics & Human Disease Laboratory, Department of Life Sciences, Shiv Nadar University, Uttar PradeshAbstract Background Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment. Methods The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-β-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library. Results Among all the compounds screened, 1-aryltetrahydro-β-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds. Conclusion Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.https://doi.org/10.1186/s12936-021-03632-2PlasmodiumArtemisininArtemisinin-resistanceDOSIndole |
| spellingShingle | Akshaykumar Nayak Himani Saxena Chandramohan Bathula Tarkeshwar Kumar Souvik Bhattacharjee Subhabrata Sen Ashish Gupta Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum Malaria Journal Plasmodium Artemisinin Artemisinin-resistance DOS Indole |
| title | Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum |
| title_full | Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum |
| title_fullStr | Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum |
| title_full_unstemmed | Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum |
| title_short | Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum |
| title_sort | diversity oriented synthesis derived indole based spiro and fused small molecules kills artemisinin resistant plasmodium falciparum |
| topic | Plasmodium Artemisinin Artemisinin-resistance DOS Indole |
| url | https://doi.org/10.1186/s12936-021-03632-2 |
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