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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Pranab K. Bhadra, Rachael N. Magwaza, Niroshini Nirmalan, Sally Freeman, Jill Barber, Biljana Arsic
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	erythromycin B derivatives anti-malarial activity conformational search molecular docking interactions Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85
Acceso en línea:	https://doaj.org/article/9cc1e0206ad54b88a9de8782a4d6b89f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:9cc1e0206ad54b88a9de8782a4d6b89f
record_format	dspace
spelling	oai:doaj.org-article:9cc1e0206ad54b88a9de8782a4d6b89f2021-11-25T18:15:26ZSelected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies10.3390/ma142269801996-1944https://doaj.org/article/9cc1e0206ad54b88a9de8782a4d6b89f2021-11-01T00:00:00Zhttps://www.mdpi.com/1996-1944/14/22/6980https://doaj.org/toc/1996-1944Erythromycin 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.Pranab K. BhadraRachael N. MagwazaNiroshini NirmalanSally FreemanJill BarberBiljana ArsicMDPI AGarticleerythromycin B derivativesanti-malarial activityconformational searchmolecular dockinginteractionsTechnologyTElectrical engineering. Electronics. Nuclear engineeringTK1-9971Engineering (General). Civil engineering (General)TA1-2040MicroscopyQH201-278.5Descriptive and experimental mechanicsQC120-168.85ENMaterials, Vol 14, Iss 6980, p 6980 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	erythromycin B derivatives anti-malarial activity conformational search molecular docking interactions Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85
spellingShingle	erythromycin B derivatives anti-malarial activity conformational search molecular docking interactions Technology T Electrical engineering. Electronics. Nuclear engineering TK1-9971 Engineering (General). Civil engineering (General) TA1-2040 Microscopy QH201-278.5 Descriptive and experimental mechanics QC120-168.85 Pranab K. Bhadra Rachael N. Magwaza Niroshini Nirmalan Sally Freeman Jill Barber Biljana Arsic Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies
description	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.
format	article
author	Pranab K. Bhadra Rachael N. Magwaza Niroshini Nirmalan Sally Freeman Jill Barber Biljana Arsic
author_facet	Pranab K. Bhadra Rachael N. Magwaza Niroshini Nirmalan Sally Freeman Jill Barber Biljana Arsic
author_sort	Pranab K. Bhadra
title	Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies
title_short	Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies
title_full	Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies
title_fullStr	Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies
title_full_unstemmed	Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies
title_sort	selected derivatives of erythromycin b-<i>in silico</i> and anti-malarial studies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9cc1e0206ad54b88a9de8782a4d6b89f
work_keys_str_mv	AT pranabkbhadra selectedderivativesoferythromycinbiinsilicoiandantimalarialstudies AT rachaelnmagwaza selectedderivativesoferythromycinbiinsilicoiandantimalarialstudies AT niroshininirmalan selectedderivativesoferythromycinbiinsilicoiandantimalarialstudies AT sallyfreeman selectedderivativesoferythromycinbiinsilicoiandantimalarialstudies AT jillbarber selectedderivativesoferythromycinbiinsilicoiandantimalarialstudies AT biljanaarsic selectedderivativesoferythromycinbiinsilicoiandantimalarialstudies
_version_	1718411453866704896

Selected Derivatives of Erythromycin B-<i>In Silico</i> and Anti-Malarial Studies

Ejemplares similares