Hemisynthetic alkaloids derived from trilobine are antimalarials with sustained activity in multidrug-resistant .

Malaria eradication requires the development of new drugs to combat drug-resistant parasites. We identified bisbenzylisoquinoline alkaloids isolated from that are active against blood stages. Synthesis of a library of 94 hemi-synthetic derivatives allowed to identify compound that kills multi-drug resistant clinical isolates in the nanomolar range (median IC ranging from 35 to 88 nM).

Identification of Chemical Probes Targeting MBD2.

Epigenetics has received much attention in the past decade. Many insights on epigenetic (dys)regulation in diseases have been obtained, and clinical therapies targeting them are in place. However, the readers of the epigenetic marks are lacking enlightenment behind this revolution, and it is poorly understood how DNA methylation is being read and translated to chromatin function and cellular responses.

Quinazoline-based analog of adenine as an antidote against MLL-rearranged leukemia cells: synthesis, inhibition assays and docking studies.

Post-translational modifications of histones constitute a dynamic process impacting gene expression. A well-studied modification is lysine methylation. Among the lysine histone methyltransferases, DOT1L is implicated in various diseases, making it a very interesting target for drug discovery.

Procainamide-SAHA Fused Inhibitors of hHDAC6 Tackle Multidrug-Resistant Malaria Parasites.

Epigenetic post-translational modifications are essential for human malaria parasite survival and progression through its life cycle. Here, we present new functionalized suberoylanilide hydroxamic acid (SAHA) derivatives that chemically combine the pan-histone deacetylase inhibitor SAHA with the DNA methyltransferase inhibitor procainamide. A three- or four-step chemical synthesis was designed starting from cheap raw materials.