Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2
Following a structure-based virtual screening, a series of 2,4 thiazolidinediones was synthesized in order to explore structure activity relationships for inhibition of the Plasmodium falciparum cysteine protease falcipain-2 (FP-2) and of whole cell antiparasitic activity. Most compounds exhibited l...
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| Format: | Article |
| Language: | English |
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Elsevier
2022
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| Online Access: | https://doi.org/10.1016/j.ejmech.2014.11.061 http://hdl.handle.net/11408/4923 |
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| author | Sharma, Rajni Kant Younis, Yassir Mugumbate, Grace Njoroge, Mathew Gut, Jiri Rosenthal, Philip J Chibale, Kelly |
| author_facet | Sharma, Rajni Kant Younis, Yassir Mugumbate, Grace Njoroge, Mathew Gut, Jiri Rosenthal, Philip J Chibale, Kelly |
| author_sort | Sharma, Rajni Kant |
| collection | DSpace |
| description | Following a structure-based virtual screening, a series of 2,4 thiazolidinediones was synthesized in order to explore structure activity relationships for inhibition of the Plasmodium falciparum cysteine protease falcipain-2 (FP-2) and of whole cell antiparasitic activity. Most compounds exhibited low micromolar antiplasmodial activities against the P. falciparum drug resistant W2 strain. The most active compounds of the series were tested for in vitro microsomal metabolic stability and found to be susceptible to hepatic metabolism. Subsequent metabolite identification studies highlighted the metabolic hot spots. Molecular docking studies of a frontrunner inhibitor were carried out to determine the probable binding mode of this class of inhibitors in the active site of FP-2. |
| format | Article |
| id | ir-11408-4923 |
| institution | My University |
| language | English |
| publishDate | 2022 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | ir-11408-49232022-06-28T12:30:24Z Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2 Sharma, Rajni Kant Younis, Yassir Mugumbate, Grace Njoroge, Mathew Gut, Jiri Rosenthal, Philip J Chibale, Kelly Antiplasmodial agents Falcipain-2 Thiazolidinone Following a structure-based virtual screening, a series of 2,4 thiazolidinediones was synthesized in order to explore structure activity relationships for inhibition of the Plasmodium falciparum cysteine protease falcipain-2 (FP-2) and of whole cell antiparasitic activity. Most compounds exhibited low micromolar antiplasmodial activities against the P. falciparum drug resistant W2 strain. The most active compounds of the series were tested for in vitro microsomal metabolic stability and found to be susceptible to hepatic metabolism. Subsequent metabolite identification studies highlighted the metabolic hot spots. Molecular docking studies of a frontrunner inhibitor were carried out to determine the probable binding mode of this class of inhibitors in the active site of FP-2. 2022-06-28T12:30:24Z 2022-06-28T12:30:24Z 2015 Article 0223-5234 https://doi.org/10.1016/j.ejmech.2014.11.061 http://hdl.handle.net/11408/4923 en European Journal of Medicinal Chemistry;90; Pages 507-518 open Elsevier |
| spellingShingle | Antiplasmodial agents Falcipain-2 Thiazolidinone Sharma, Rajni Kant Younis, Yassir Mugumbate, Grace Njoroge, Mathew Gut, Jiri Rosenthal, Philip J Chibale, Kelly Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2 |
| title | Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2 |
| title_full | Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2 |
| title_fullStr | Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2 |
| title_full_unstemmed | Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2 |
| title_short | Synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2 |
| title_sort | synthesis and structure-activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the plasmodium falciparum cysteine protease falcipain-2 |
| topic | Antiplasmodial agents Falcipain-2 Thiazolidinone |
| url | https://doi.org/10.1016/j.ejmech.2014.11.061 http://hdl.handle.net/11408/4923 |
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