Background: Malaria greatly affects the world health, having caused more than 228 million
cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating
the need for the development of new antimalarial drugs.
Objective: Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived from isocoumarins
and a 3,4-dihydroisocoumarin.
Methods: The compounds were synthesized in 4 to 6-step reactions with the formation of the triazole
ring via the Copper(I)-catalyzed 1,3-dipolar cycloaddition between isocoumarin or 3,4-
dihydroisocoumarin azides and terminal alkynes. This key reaction provided compounds with an unprecedented
connection of isocoumarin or 3,4-dihydroisocoumarin and the 1,2,3-triazole ring. The products
were tested for their antiplasmodial activity against a Plasmodium falciparum chloroquine resistant
and sensitive strains (W2 and 3D7, respectively).
Results: Thirty-one substances were efficiently obtained by the proposed routes with an overall yield of
25-53%. The active substances in the antiplasmodial test displayed IC50 values ranging from 0.68-2.89
μM and 0.85-2.07 μM against W2 and 3D7 strains, respectively.
Conclusion: This study demonstrated the great potential of isocoumarin or 3,4-dihydroisocoumarin derivatives
because practically all the tested substances were active against Plasmodium falciparum.