Marine Guanidine Alkaloids Inhibit Malaria Parasites Development in In Vitro, In Vivo and Ex Vivo Assays.

Malaria is a disease caused by pathogenic protozoa Plasmodium spp., with a significant global impact on human health. Increasing resistance of P. falciparum strains to drugs treating malaria highlights the urgent need for the discovery of new antimalarial candidates. Batzelladines are marine guanidine alkaloids that exhibit potent antiparasitic activity. Herein, results of the parasitological profiling assessment of batzelladines F and L are reported. Both compounds exhibited potent antiplasmodial activity, moderate cytotoxicity, and suitable selectivity indexes. Batzelladines F and L are fast-acting P. falciparum inhibitors, with a pronounced inhibitory activity against resistant strains and laboratory-adapted clinical isolates of P. falciparum. Batzelladines F and L also demonstrated ex vivo activity against clinical isolates of P. falciparum and P. vivax, and batzelladine F showed in vivo antimalarial activity in a P. berghei malaria model. The results reported constitute a robust rationale for the development of guanidine alkaloid derivatives as lead candidates for malaria treatment.