Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin-HDAC Inhibitor Hybrids as Multitarget Drugs.

ABSTRACT: Artemisinin-based combination therapies (ACTs) are the gold standard for the treatment of malaria, but the efficacy is threatened by the development of parasite resistance. Histone deacetylase inhibitors (HDACis) are an emerging new class of potential antiplasmodial drugs. In this work, we present the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin-HDACi hybrid molecules. The screening of the hybrid molecules for their activity against selected human HDAC isoforms, asexual blood stage P. falciparum parasites, and a panel of leukemia cell lines delivered important structure-activity relationships. All synthesized compounds demonstrated potent activity against the 3D7 and Dd2 line of P. falciparum with IC₅₀ values in the single-di

SUBMITTER: von Bredow L 

PROVIDER: S-EPMC8952208 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature