In Vitro Activity of wALADin Benzimidazoles against Different Life Cycle Stages of Plasmodium Parasites

Abstract

c wALADin1 benzimidazoles are specific inhibitors of ␦-aminolevulinic acid dehydratase from Wolbachia endobacteria of filarial nematodes. We report that wALADin1 and two derivatives killed blood stage Plasmodium falciparum in vitro (50% inhibitory concentrations, 39, 7.7, and 12.8 M, respectively). One of these derivatives inhibited gliding motility of Plasmodium berghei ANKA infectious sporozoites with nanomolar affinity and blocked invasion into hepatocytes but did not affect intrahepatocytic replication. Hence, wALADin1 benzimidazoles are tools to study gliding motility and potential antiplasmodial drug candidates.

Active migration and passive transport of malaria parasites

“…For example, if one targets a conserved motility mechanism by a drug, this could likewise block active migration of sporozoites, invasion of erythrocytes by merozoites, or ookinete motility [79]. There are indeed suggestions in the literature that low molecular weight molecules could be used to stop active parasite movement [80][81][82][83][84][85][86]. Perhaps potent and parasite-selective inhibitors could be developed for formulation in topical insect-repellant creams that would serve as a malaria prophylaxis strategy.…”

Synergistic blending of high-valued heterocycles inhibits growth of Plasmodium falciparum in culture and P. berghei infection in mouse model

“…The presence of additional high-valued bioactive heterocycles may intensify the efficacy of the Phts. The broad spectrum pharmacological properties 23 – 25 and antimalarial activities 26 – 29 of benzimidazole and triazole heterocycles created the interest in the unification of these examined scaffolds into a single molecule. As a part of our ongoing efforts and diverse therapeutic efficiency of these heterocycles, we report here the design of synergistic association of Pht, benzimidazole and flexible triazoles anticipating new analogues as new entry for antimalarial chemotherapy.…”