posted on 2021-03-06, 01:15authored byMeta Leshabane, Godwin Akpeko Dziwornu, Dina Coertzen, Janette Reader, Phanankosi Moyo, Mariëtte van der Watt, Kelly Chisanga, Consolata Nsanzubuhoro, Richard Ferger, Erica Erlank, Nelius Venter, Lizette Koekemoer, Kelly Chibale, Lyn-Marie Birkholtz
The continued emergence
of resistance to front-line antimalarial
treatments is of great concern. Therefore, new compounds that potentially
have a novel target in various developmental stages of Plasmodium parasites are needed to treat patients and halt the spread of malaria.
Here, several benzimidazole derivatives were screened for activity
against the symptom-causing intraerythrocytic asexual blood stages
and the transmissible gametocyte stages of P. falciparum. Submicromolar activity was obtained for 54 compounds against asexual
blood stage parasites with 6 potent at IC50 < 100 nM
while not displaying any marked toxicity against mammalian cells.
Nanomolar potency was also observed against gametocytes with two compounds
active against early stage gametocytes and two compounds active against
late-stage gametocytes. The transmission-blocking potential of the
latter was confirmed as they could prevent male gamete exflagellation
and the lead compound reduced transmission by 72% in an in
vivo mosquito feeding model. These compounds therefore have
activity against multiple stages of Plasmodium parasites
with potential for differential targets.