The WHO 2022 Malaria Report, estimated 247 million cases and 619,000 deaths with the majority of infants under-five caused by malaria. Efforts to control the disease have decreased significantly the burden since 2000; however, this progression seems to be stalled during the last four years.
Based on the potential of macrocycles and on our previous work, we obtained tetra, penta and hexacyclopeptides, containing N-methyl amino acids to evaluate how N-methylation and/or the ring size affect the bioactivity of cyclopeptidic antimalarial compounds.
The syntheses of peptides by SPPS (Solid Phase Peptide Synthesis), the solution or on-resin macrocyclization using two methodologies,the activity and selectivity against the P. falciparum were performed. Several compounds showed subnanomolar or nanomolar EC50 and high selectivity. Furthermore, two cyclopeptides have confirmed in vivo efficacy after oral administration. New investigations allowed us to obtain 4 polymeric nanoparticles containing active compounds that are being tested.
