Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships
Piperazine and pyrrolidine derivatives were synthesized and evaluated for their capacity to inhibit the growth of Plasmodium falciparum chloroquine-resistant (FCR-3) strain in culture. The combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmod...
| Main Authors: | , , , , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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Elsevier
2011
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/18730 |
| _version_ | 1793400187425652736 |
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| author | Mendoza, A. (Adela) Pérez-Silanes, S. (Silvia) Quiliano, M. (Miguel) Pabon, A. (Adriana) Gonzalez, G. (Germán) Garavito, G. (Giovanny) Zimic, M. (Mirko) Vaisberg, A. (Abrahm) Aldana, I. (Ignacio) Monge, A. (Antonio) Deharo, E. (Eric) |
| author_facet | Mendoza, A. (Adela) Pérez-Silanes, S. (Silvia) Quiliano, M. (Miguel) Pabon, A. (Adriana) Gonzalez, G. (Germán) Garavito, G. (Giovanny) Zimic, M. (Mirko) Vaisberg, A. (Abrahm) Aldana, I. (Ignacio) Monge, A. (Antonio) Deharo, E. (Eric) |
| author_sort | Mendoza, A. (Adela) |
| collection | DSpace |
| description | Piperazine and pyrrolidine derivatives were synthesized and evaluated for their capacity to inhibit the growth of Plasmodium falciparum chloroquine-resistant (FCR-3) strain in culture. The combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmodial activity. Five compounds of the aryl-alcohol series inhibited 50% of parasite growth at doses ≤ 10 µM. The most active compound 1-(4-fluoronaphthyl)-3-[4-(4-nitro-2-trifluoromethylphenyl)piperazin-1-yl]propan-1-ol was almost 20 to 40 times more active on Plasmodium falciparum (IC50: 0.5 µM) than on tumorogenic and non tumorogenic cells. Calculated physicochemical parameters showed a good potential for intestinal absorption, but due to difficulty in being solubilised prior to oral administration, it was weakly active against Plasmodium berghei infected mice (ED50: 35%). In silico molecular docking study and molecular electrostatic potential calculation revealed that this compound bound to the active site of Plasmodium plasmepsin II enzyme. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-18730 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2011 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-187302020-03-04T02:46:38Z Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships Mendoza, A. (Adela) Pérez-Silanes, S. (Silvia) Quiliano, M. (Miguel) Pabon, A. (Adriana) Gonzalez, G. (Germán) Garavito, G. (Giovanny) Zimic, M. (Mirko) Vaisberg, A. (Abrahm) Aldana, I. (Ignacio) Monge, A. (Antonio) Deharo, E. (Eric) Piperazine Pyrrolidine Antiplasmodial Plasmodium Antimalarial agents Docking studies Piperazine and pyrrolidine derivatives were synthesized and evaluated for their capacity to inhibit the growth of Plasmodium falciparum chloroquine-resistant (FCR-3) strain in culture. The combined presence of a hydroxyl group, a propane chain and a fluor were shown to be crucial for the antiplasmodial activity. Five compounds of the aryl-alcohol series inhibited 50% of parasite growth at doses ≤ 10 µM. The most active compound 1-(4-fluoronaphthyl)-3-[4-(4-nitro-2-trifluoromethylphenyl)piperazin-1-yl]propan-1-ol was almost 20 to 40 times more active on Plasmodium falciparum (IC50: 0.5 µM) than on tumorogenic and non tumorogenic cells. Calculated physicochemical parameters showed a good potential for intestinal absorption, but due to difficulty in being solubilised prior to oral administration, it was weakly active against Plasmodium berghei infected mice (ED50: 35%). In silico molecular docking study and molecular electrostatic potential calculation revealed that this compound bound to the active site of Plasmodium plasmepsin II enzyme. 2011-07-04T17:59:16Z 2011-07-04T17:59:16Z 2011 info:eu-repo/semantics/article https://hdl.handle.net/10171/18730 eng info:eu-repo/semantics/openAccess application/pdf Elsevier |
| spellingShingle | Piperazine Pyrrolidine Antiplasmodial Plasmodium Antimalarial agents Docking studies Mendoza, A. (Adela) Pérez-Silanes, S. (Silvia) Quiliano, M. (Miguel) Pabon, A. (Adriana) Gonzalez, G. (Germán) Garavito, G. (Giovanny) Zimic, M. (Mirko) Vaisberg, A. (Abrahm) Aldana, I. (Ignacio) Monge, A. (Antonio) Deharo, E. (Eric) Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships |
| title | Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships |
| title_full | Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships |
| title_fullStr | Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships |
| title_full_unstemmed | Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships |
| title_short | Aryl piperazine and pyrrolidine as antimalarial agents. Synthesis and investigation of structure-activity relationships |
| title_sort | aryl piperazine and pyrrolidine as antimalarial agents. synthesis and investigation of structure-activity relationships |
| topic | Piperazine Pyrrolidine Antiplasmodial Plasmodium Antimalarial agents Docking studies |
| url | https://hdl.handle.net/10171/18730 |
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