3H-1,5-benzodiazepines show micromolar antimalarial activity; PfSET3 floated as target
- Eighteen new 3H-1,5-benzodiazepines were made and tested against chloroquine-sensitive and resistant P. falciparum strains, with HepG2 cytotoxicity as a first selectivity check.
- Several compounds were active in the low micromolar range, with different members showing the best potency and the best selectivity.
- The two leads were only weak inhibitors of human G9a; docking, MM-GBSA and MD were used to propose binding to parasite PfSET3.
💡 Points
Low-micromolar whole-cell activity with a thin selectivity window is a start, not a lead; the target claim rests on docking, which I'd treat as a hypothesis only. What I like is the unusual chemotype against a parasite epigenetic enzyme. Next I'd want a biochemical PfSET3 assay and some SAR around the best-selectivity compound.