New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation
Two series of pyrazol and propenone quinoxaline derivatives were tested for parasiticidal activity (against amastigotes of Leishmania peruviana and trypomastigotes of Trypanosoma cruzi) and for toxicity against proliferative and non-proliferative cells. The pyrazol series was almost inactive against...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | info:eu-repo/semantics/article |
| Language: | eng |
| Published: |
Elsevier
2014
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10171/35791 |
| _version_ | 1793400193233715200 |
|---|---|
| author | Estevez, Y. (Yannick) Quiliano, M. (Miguel) Burguete, A. (Asunción) Cabanillas, B. (Billy) Zimic, M. (Mirko) Malaga, E. (Edith) Verastegui, M. (Manuela) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Castillo, D. (Denis) Deharo, E. (Eric) |
| author_facet | Estevez, Y. (Yannick) Quiliano, M. (Miguel) Burguete, A. (Asunción) Cabanillas, B. (Billy) Zimic, M. (Mirko) Malaga, E. (Edith) Verastegui, M. (Manuela) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Castillo, D. (Denis) Deharo, E. (Eric) |
| author_sort | Estevez, Y. (Yannick) |
| collection | DSpace |
| description | Two series of pyrazol and propenone quinoxaline derivatives were tested for parasiticidal activity (against amastigotes of Leishmania peruviana and trypomastigotes of Trypanosoma cruzi) and for toxicity against proliferative and non-proliferative cells. The pyrazol series was almost inactive against T. cruzi but, 2,6-Dimethyl-3-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-1H-pyrazol-3-yl] - quinoxaline 1,4-dioxide inhibited 50% of Leishmania growth at 8.9 µM with no impact against proliferative kidney cells and low toxicity against Thp-1 and murine macrophages. The compounds of the propenone series were moderately active against T. cruzi. Among them, 2 compounds were particularly interesting: (2E)-1-(7-Fluoro-3-methyl-quinoxalin-2-yl)-3-(3,4,5-trimethoxy-phenyl)-propenone, that showed a selective activity against proliferative cells (cancer and parasites), being inactive against normal murine peritoneal macrophages and (2E)-3-(3,4,5-Trimethoxy-phenyl)-1-(3,6,7-trimethyl-quinoxalin-2-yl)-propenone that was only active against Leishmania and inactive against the other tested cells. Furthermore in silico studies were performed for ADME properties and docking studies, both series of compounds respected the Lipinski’s rules and show linear correlation between tripanosomaticidal activities and LogP. Docking studies revealed that compounds of the second series could interact with the poly (ADP-ribose) polymerase protein of Trypanosoma cruzi. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-35791 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-357912020-03-04T00:13:54Z New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation Estevez, Y. (Yannick) Quiliano, M. (Miguel) Burguete, A. (Asunción) Cabanillas, B. (Billy) Zimic, M. (Mirko) Malaga, E. (Edith) Verastegui, M. (Manuela) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Castillo, D. (Denis) Deharo, E. (Eric) Quinoxaline Leishmania peruviana Trypanosoma cruzi Two series of pyrazol and propenone quinoxaline derivatives were tested for parasiticidal activity (against amastigotes of Leishmania peruviana and trypomastigotes of Trypanosoma cruzi) and for toxicity against proliferative and non-proliferative cells. The pyrazol series was almost inactive against T. cruzi but, 2,6-Dimethyl-3-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-1H-pyrazol-3-yl] - quinoxaline 1,4-dioxide inhibited 50% of Leishmania growth at 8.9 µM with no impact against proliferative kidney cells and low toxicity against Thp-1 and murine macrophages. The compounds of the propenone series were moderately active against T. cruzi. Among them, 2 compounds were particularly interesting: (2E)-1-(7-Fluoro-3-methyl-quinoxalin-2-yl)-3-(3,4,5-trimethoxy-phenyl)-propenone, that showed a selective activity against proliferative cells (cancer and parasites), being inactive against normal murine peritoneal macrophages and (2E)-3-(3,4,5-Trimethoxy-phenyl)-1-(3,6,7-trimethyl-quinoxalin-2-yl)-propenone that was only active against Leishmania and inactive against the other tested cells. Furthermore in silico studies were performed for ADME properties and docking studies, both series of compounds respected the Lipinski’s rules and show linear correlation between tripanosomaticidal activities and LogP. Docking studies revealed that compounds of the second series could interact with the poly (ADP-ribose) polymerase protein of Trypanosoma cruzi. 2014-04-12T17:22:07Z 2014-04-12T17:22:07Z 2011-01-25 info:eu-repo/semantics/article https://hdl.handle.net/10171/35791 eng info:eu-repo/semantics/openAccess application/pdf Elsevier |
| spellingShingle | Quinoxaline Leishmania peruviana Trypanosoma cruzi Estevez, Y. (Yannick) Quiliano, M. (Miguel) Burguete, A. (Asunción) Cabanillas, B. (Billy) Zimic, M. (Mirko) Malaga, E. (Edith) Verastegui, M. (Manuela) Pérez-Silanes, S. (Silvia) Aldana, I. (Ignacio) Monge, A. (Antonio) Castillo, D. (Denis) Deharo, E. (Eric) New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation |
| title | New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation |
| title_full | New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation |
| title_fullStr | New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation |
| title_full_unstemmed | New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation |
| title_short | New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation |
| title_sort | new quinoxaline 1,4-di-n-oxide derivatives: trypanosomaticidal activities and enzyme docking simulation |
| topic | Quinoxaline Leishmania peruviana Trypanosoma cruzi |
| url | https://hdl.handle.net/10171/35791 |
| work_keys_str_mv | AT estevezyyannick newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT quilianommiguel newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT burgueteaasuncion newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT cabanillasbbilly newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT zimicmmirko newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT malagaeedith newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT verasteguimmanuela newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT perezsilanesssilvia newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT aldanaiignacio newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT mongeaantonio newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT castilloddenis newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation AT deharoeeric newquinoxaline14dinoxidederivativestrypanosomaticidalactivitiesandenzymedockingsimulation |