Synthesis, in vitro antiplasmodial activity and cytotoxicity of a series of artemisinin–triazine hybrids and hybrid-dimers

• Synthesis of a series of artemisinin–triazine hybrids and hybrid-dimers.
• Evaluation of antimalarial activity of series.
• Hybrid-dimers are more active than hybrids.
• Hybrid-dimers were as potent as artesunate against Dd2 strain.

A series of artemisinin–triazine hybrids and hybrid-dimers were synthesized and their in vitro antimalarial activity against the chloroquine sensitive (CQS), the gametocytocidal (NF54) and the choroquine resistant (CQR) Dd2 strains of Plasmodium falciparum determined, while their toxicity against CHO cells were also established. These compounds were prepared by linking artemisinin and triazine pharmacophores through nucleophilic substitution, using conventional and microwave assisted methods. These hybrids and hybrid-dimers were all found to be active against all three Plasmodium strains, with the p-anisidino-substituted triazine hybrid-dimer 22 being the most active of all. It showed good antigametocytocidal activity against the NF54 strain, with a 50% inhibitory concentration value in the nanomolar range, while having a potency comparable to that of artesunate against the Dd2 strain. This hybrid-dimer further demonstrated selective toxicity towards the parasitic cells. This dimer hence showed the necessary potential as candidate for further investigation in the search for malaria transmission blocking drugs so desperately needed.

Series of artemisinin–triazine hybrids and hybrid-dimers were synthesized and their in vitro antimalarial activity against NF54 and Dd2 strains of Plasmodium falciparum as well as cytotoxicity against CHO cells were determined.Figure optionsDownload as PowerPoint slide