Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies
Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their...
Guardado en:
| Autores principales: | , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9cc1e0206ad54b88a9de8782a4d6b89f |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| Sumario: | Erythromycin A is an established anti-bacterial agent against Gram-positive bacteria, but it is unstable to acid. This led to an evaluation of erythromycin B and its derivatives because these have improved acid stability. These compounds were investigated for their anti-malarial activities, by their <i>in silico</i> molecular docking into segments of the exit tunnel of the apicoplast ribosome from <i>Plasmodium falciparum</i>. This is believed to be the target of the erythromycin A derivative, azithromycin, which has mild anti-malarial activity. The erythromycin B derivatives were evaluated on the multi-drug (chloroquine, pyrimethamine, and sulfadoxine)-resistant strain K1 of <i>P. falciparum</i> for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of <i>P. falciparum</i> with low micro-molar IC<sub>50</sub> values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC<sub>50</sub> of 68.6 µM, <i>d</i>-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of <i>P. falciparum</i>. Based on the molecular docking, it seems that a small number of favourable interactions or the presence of unfavourable interactions of investigated derivatives of erythromycin B with <i>in silico</i> constructed segment from the exit tunnel from the apicoplast of <i>P</i>. <i>falciparum</i> is the reason for their weak in vitro anti-malarial activities. |
|---|