New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum.

ABSTRACT:

Background

The emergence and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy in Southeast Asia prompted the need to develop new endoperoxide-type drugs.

Methods

A chemically diverse library of endoperoxides was designed and synthesized. The compounds were screened for in vitro and in vivo anti-malarial activity using, respectively, the SYBR Green I assay and a mouse model. Ring survival and mature stage survival assays were performed against artemisinin-resistant and artemisinin-sensitive P. falciparum strains. Cytotoxicity was evaluated against mammalian cell lines V79 and HepG2, using the MTT assay.

Results

The synthesis and anti-malarial activity of 21 new endoperoxide-derived compounds is reported, where the peroxide pharmacopho

SUBMITTER: Lobo L 

PROVIDER: S-EPMC5883364 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature