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Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives
BACKGROUND: The search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malar...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396901/ https://www.ncbi.nlm.nih.gov/pubmed/35996135 http://dx.doi.org/10.1186/s12936-022-04266-8 |
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author | Ibezim, Akachukwu Ofokansi, Martha N. Ndukwe, Xavier Chiama, Chidera S. Obi, Bonaventure C. Isiogugu, Ogechukwu N. Ikechukwu, Peter E. Onwuka, Akachukwu M. Ihim, Stella A. Asegbeloyin, Jonnie N. Nwodo, Ngozi J. |
author_facet | Ibezim, Akachukwu Ofokansi, Martha N. Ndukwe, Xavier Chiama, Chidera S. Obi, Bonaventure C. Isiogugu, Ogechukwu N. Ikechukwu, Peter E. Onwuka, Akachukwu M. Ihim, Stella A. Asegbeloyin, Jonnie N. Nwodo, Ngozi J. |
author_sort | Ibezim, Akachukwu |
collection | PubMed |
description | BACKGROUND: The search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malarial property. METHODS: Here, in vivo prophylactic and curative activities of the compounds were assessed while their binding affinity for falcipain-2, a crucial enzyme in Plasmodium survival, was done using computational techniques. RESULTS: The two derivatives (BepINH and BepBeH) respectively led to a significant (p < 0.05) reduction in parasitaemia count (0.76 ± 1.11 and 0.79 ± 1.19) at day 3 post-treatment relative to the negative control (16.37 ± 1.25). For the prophylactic study, it was observed that the highest parasitaemia suppression level of 95.35% and 95.17% for BepINH and BepBeH at 15 mg/kg was slightly comparable to that obtained for ACT-Lonart (99.38%). In addition, their haematological profiles indicate that they are potentially beneficial in suppressing haemolytic damage to RBC, thereby protecting the body against infection-induced anaemia. Docking calculations on the derivatives toward the Plasmodium falciparum falcipain-2 revealed that they favourably interacted with a binding affinity higher than that of a known cocrystallized inhibitor. CONCLUSION: This study confirms the relevance of multi-functional molecules in the search for new and effective anti-plasmodial agent and lay the foundation for further development of these compound series to potent anti-plasmodial agent that interacts with falcipain-2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-022-04266-8. |
format | Online Article Text |
id | pubmed-9396901 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93969012022-08-24 Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives Ibezim, Akachukwu Ofokansi, Martha N. Ndukwe, Xavier Chiama, Chidera S. Obi, Bonaventure C. Isiogugu, Ogechukwu N. Ikechukwu, Peter E. Onwuka, Akachukwu M. Ihim, Stella A. Asegbeloyin, Jonnie N. Nwodo, Ngozi J. Malar J Research BACKGROUND: The search for pharmacologically effective agents among molecules bearing multiple functionalities is commonly practiced. In continuation of the search for new anti-malarial agents, new pyrazole-hydrazine coupled Schiff-base derivatives previously synthesized were screened for anti-malarial property. METHODS: Here, in vivo prophylactic and curative activities of the compounds were assessed while their binding affinity for falcipain-2, a crucial enzyme in Plasmodium survival, was done using computational techniques. RESULTS: The two derivatives (BepINH and BepBeH) respectively led to a significant (p < 0.05) reduction in parasitaemia count (0.76 ± 1.11 and 0.79 ± 1.19) at day 3 post-treatment relative to the negative control (16.37 ± 1.25). For the prophylactic study, it was observed that the highest parasitaemia suppression level of 95.35% and 95.17% for BepINH and BepBeH at 15 mg/kg was slightly comparable to that obtained for ACT-Lonart (99.38%). In addition, their haematological profiles indicate that they are potentially beneficial in suppressing haemolytic damage to RBC, thereby protecting the body against infection-induced anaemia. Docking calculations on the derivatives toward the Plasmodium falciparum falcipain-2 revealed that they favourably interacted with a binding affinity higher than that of a known cocrystallized inhibitor. CONCLUSION: This study confirms the relevance of multi-functional molecules in the search for new and effective anti-plasmodial agent and lay the foundation for further development of these compound series to potent anti-plasmodial agent that interacts with falcipain-2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12936-022-04266-8. BioMed Central 2022-08-22 /pmc/articles/PMC9396901/ /pubmed/35996135 http://dx.doi.org/10.1186/s12936-022-04266-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Ibezim, Akachukwu Ofokansi, Martha N. Ndukwe, Xavier Chiama, Chidera S. Obi, Bonaventure C. Isiogugu, Ogechukwu N. Ikechukwu, Peter E. Onwuka, Akachukwu M. Ihim, Stella A. Asegbeloyin, Jonnie N. Nwodo, Ngozi J. Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives |
title | Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives |
title_full | Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives |
title_fullStr | Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives |
title_full_unstemmed | Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives |
title_short | Evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to Schiff base derivatives |
title_sort | evaluation of anti-malarial potency of new pyrazole-hydrazine coupled to schiff base derivatives |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9396901/ https://www.ncbi.nlm.nih.gov/pubmed/35996135 http://dx.doi.org/10.1186/s12936-022-04266-8 |
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