Design, Synthesis and Evaluation of Bifunctional Acridinine-Naphthalenediimide Redox-Active Conjugates as Antimalarials.

ABSTRACT: A novel class of bifunctional molecules was synthesized integrating acridine (Ac) and redox-active naphthalenediimide (NDI) scaffolds directly and through a flexible linker (en). We evaluated in vitro antiplasmodial activity, physicochemical properties, and a possible mode of action. Theoretical studies suggested electronic segmentation between the electron-rich Ac and electron-deficient NDI scaffolds. Orthogonal Ac-NDI molecules showed activities in the micromolar to submicromolar range against a chloroquine (CQ)-sensitive strain of human malaria pathogen Plasmodium falciparum (maximum activity, IC₅₀: 0.419 μM). The flexible Ac-en-NDI molecules were most potent and showed activity in the nanomolar range against both CQ-sensitive (with most effective compounds, IC_50<

SUBMITTER: Dana S 

PROVIDER: S-EPMC6044610 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature