Retargeting azithromycin analogues to have dual-modality antimalarial activity.

ABSTRACT:

Background

Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium spp. malaria parasites is urgently needed. Azithromycin is a clinically used macrolide antibiotic proposed as a partner drug for combination therapy in malaria, which has also been tested as monotherapy. However, its slow-killing 'delayed-death' activity against the parasite's apicoplast organelle and suboptimal activity as monotherapy limit its application as a potential malaria treatment. Here, we explore a panel of azithromycin analogues and demonstrate that chemical modifications can be used to greatly improve the speed and potency of antimalarial action.

Results

Investigation of 84 azithromycin an

SUBMITTER: Burns AL 

PROVIDER: S-EPMC7526119 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature