Leishmaniasis refers
to a collection of diseases caused
by protozoa
from the Leishmania genus. These diseases, along
with other parasitic afflictions, pose a significant public health
issue, particularly given the escalating number of at-risk patients.
This group includes immunocompromised individuals and those residing
in impoverished conditions. The treatment of leishmaniasis is crucial,
particularly in light of the mortality rate associated with nontreatment,
which stands at 20–30,000 deaths per year globally. However,
the therapeutic options currently available are limited, often ineffective,
and potentially toxic. Consequently, the pursuit of new therapeutic
alternatives is warranted. This study aims to design, synthesize,
and evaluate the leishmanicidal activity of antimicrobial peptides
functionalized with guanidine compounds and identify those with enhanced
potency and selectivity against the parasite. Accordingly, three bioconjugates
were obtained by using the solid-phase peptide synthesis protocol.
Each proved to be more potent against intracellular amastigotes than
their respective peptide or guanidine compounds alone and demonstrated
higher selectivity to the parasites than to the host cells. Thus,
the conjugation strategy employed with these compounds effectively
contributes to the development of new molecules with leishmanicidal
activity.