Selected derivatives of erythromycin B- in silico and anti-malarial studies

Bhadra, PK; Magwaza, RN; Nirmalan, NJ; Freeman, S; Barber, J; Arsic, B

Abstract

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 in silico molecular docking into segments of the exit tunnel of the apicoplast ribosome from Plasmodium falciparum. 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 P. falciparum for asexual growth inhibition on asynchronous culture. The erythromycin B derivatives were identified as active in vitro inhibitors of asexual growth of P. falciparum with low micro-molar IC50 values after a 72 h cycle. 5-Desosaminyl erythronolide B ethyl succinate showed low IC50 of 68.6 µM, d-erythromycin B 86.8 µM, and erythromycin B 9-oxime 146.0 µM on the multi-drug-resistant K1 of P. falciparum. 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 in silico constructed segment from the exit tunnel from the apicoplast of P. falciparum is the reason for their weak in vitro anti-malarial activities.

Citation

Bhadra, P., Magwaza, R., Nirmalan, N., Freeman, S., Barber, J., & Arsic, B. (2021). Selected derivatives of erythromycin B- in silico and anti-malarial studies. Materials, 14(22), e6980. https://doi.org/10.3390/ma14226980

• Journal Article Type: Article
• Acceptance Date: Nov 12, 2021
• Publication Date: Nov 18, 2021
• Deposit Date: Nov 22, 2021
• Publicly Available Date: Nov 22, 2021
• Journal: Materials
• Publisher: MDPI
• Volume: 14
• Issue: 22
• Pages: e6980
• DOI: https://doi.org/10.3390/ma14226980
• Publisher URL: https://doi.org/10.3390/ma14226980
• Related Public URLs: https://www.mdpi.com/journal/materials
• Additional Information: Additional Information : ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 1996-1944 **History: published 18-11-2021; accepted 12-11-2021; Funders : Ministry of Education, Science and Technological Development of Republic of Serbia;National Research Foundation; Grant Number: 451-03-9/2021-14/200124; Grant Number: 107881