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Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives
Malaria cases and deaths keep being excessively high every year. Some inroads gained in the last two decades have been eroded especially due to the surge of resistance to most antimalarials. The search for new molecules that can replace the ones currently in use cannot stop. In this report, the synt...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822940/ https://www.ncbi.nlm.nih.gov/pubmed/36609676 http://dx.doi.org/10.1038/s41598-022-27351-z |
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author | Escala, Nerea Pineda, Laura M. Ng, Michelle G. Coronado, Lorena M. Spadafora, Carmenza del Olmo, Esther |
author_facet | Escala, Nerea Pineda, Laura M. Ng, Michelle G. Coronado, Lorena M. Spadafora, Carmenza del Olmo, Esther |
author_sort | Escala, Nerea |
collection | PubMed |
description | Malaria cases and deaths keep being excessively high every year. Some inroads gained in the last two decades have been eroded especially due to the surge of resistance to most antimalarials. The search for new molecules that can replace the ones currently in use cannot stop. In this report, the synthesis of benzimidazole derivatives guided by structure–activity parameters is presented. Thirty-six molecules obtained are analyzed according to their activity against P. falciparum HB3 strain based on the type of substituent on rings A and B, their electron donor/withdrawing, as well as their dimension/spatial properties. There is a preference for electron donating groups on ring A, such as Me in position 5, or better, 5, 6-diMe. Ring B must be of the pyridine type such as picolinamide, other modifications are generally not favorable. Two molecules, 1 and 33 displayed antiplasmodial activity in the high nanomolar range against the chloroquine sensitive strain, with selectivity indexes above 10. Activity results of 1, 12 and 16 on a chloroquine resistance strain indicated an activity close to chloroquine for compound 1. Analysis of some of their effect on the parasites seem to suggest that 1 and 33 affect only the parasite and use a route other than interference with hemozoin biocrystallization, the route used by chloroquine and most antimalarials. |
format | Online Article Text |
id | pubmed-9822940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98229402023-01-08 Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives Escala, Nerea Pineda, Laura M. Ng, Michelle G. Coronado, Lorena M. Spadafora, Carmenza del Olmo, Esther Sci Rep Article Malaria cases and deaths keep being excessively high every year. Some inroads gained in the last two decades have been eroded especially due to the surge of resistance to most antimalarials. The search for new molecules that can replace the ones currently in use cannot stop. In this report, the synthesis of benzimidazole derivatives guided by structure–activity parameters is presented. Thirty-six molecules obtained are analyzed according to their activity against P. falciparum HB3 strain based on the type of substituent on rings A and B, their electron donor/withdrawing, as well as their dimension/spatial properties. There is a preference for electron donating groups on ring A, such as Me in position 5, or better, 5, 6-diMe. Ring B must be of the pyridine type such as picolinamide, other modifications are generally not favorable. Two molecules, 1 and 33 displayed antiplasmodial activity in the high nanomolar range against the chloroquine sensitive strain, with selectivity indexes above 10. Activity results of 1, 12 and 16 on a chloroquine resistance strain indicated an activity close to chloroquine for compound 1. Analysis of some of their effect on the parasites seem to suggest that 1 and 33 affect only the parasite and use a route other than interference with hemozoin biocrystallization, the route used by chloroquine and most antimalarials. Nature Publishing Group UK 2023-01-06 /pmc/articles/PMC9822940/ /pubmed/36609676 http://dx.doi.org/10.1038/s41598-022-27351-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Article Escala, Nerea Pineda, Laura M. Ng, Michelle G. Coronado, Lorena M. Spadafora, Carmenza del Olmo, Esther Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives |
title | Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives |
title_full | Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives |
title_fullStr | Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives |
title_full_unstemmed | Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives |
title_short | Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives |
title_sort | antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9822940/ https://www.ncbi.nlm.nih.gov/pubmed/36609676 http://dx.doi.org/10.1038/s41598-022-27351-z |
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