Bioorganometallic Compounds with Antimalarial Targets: Inhibiting Hemozoin Formation

Abstract

About half of the world's population is at risk of malaria, and in tropical countries it remains a major cause of morbidity and death in children. Drug resistance to current established antimalarial drugs such as chloroquine is driving the rise in malaria-attributed deaths. In the mid-1990s, two groupsin France and in Venezuelaprobed the potential contribution of organometallic analogues as a means of discovering new antimalarial drugs. In the present review, key topics of organometallic antimalarials are outlined using examples from the literature. The interdisciplinary research environment of bioorganometallics allows researchers to investigate the whole spectrum of the drugs' mechanisms of action. Targeting the digestive vacuole and inhibiting hemozoin formation is believed to be the main mechanism by which these drugs induce parasite death.

Blending of Soybean Oil with Selected Vegetable Oils: Impact on Oxidative Stability and Radical Scavenging Activity

“…Lipid oxidation can directly reflect shelf life of a product. Environmental factors, such as air, light and temperature, accelerate oxidative reactions which might end in the production of off-flavors and odors associated with low molecular weight volatiles, discoloration (Navarro et al, 2012). Also, oxidation induce important chemical changes of the oils that may affect directly the quality of the edible oil, generates radical oxygen species that may cause irreversible damages when reacting with biological molecules such as DNA, proteins or lipids (Bansal et al, 2010;Cabiscol et al, 2010).…”

Toward Organometallic Antischistosomal Drug Candidates

“…Since both bloodfeeding parasites, Plasmodium and Schistosoma, share the heme degradation pathway, drug candidates might interact with similar targets [34]. With this in mind, our groups in collaboration with the one of Biot used this approach and analyzed the potential of the organometallic antimalarial drug candidates ferroquine, ruthenoquine and hydroxyl-ferroquine ( Figure 2) as antischistosomal agents [35][36][37]. For comparison, the known antimalarial drugs chloroquine and mefloquine were used as reference compounds.…”

Polyamine quinoline rhodium complexes: synthesis and pharmacological evaluation as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis

“…Combination therapy is employed to delay the onset of resistance, but there have been reports of artemisinin resistance in certain parts of the world. [11][12][13] Another metal-based chloroquine complex that exhibited promising antiplasmodial activity against Plasmodium parasites is [RhCl(COD)CQ], where COD = 1,5-cyclooctadiene (Fig. A metal-based candidate, ferroquine (FQ), has demonstrated the ability to overcome resistance experienced by its parent compound, chloroquine (CQ).…”

“…8,9 It has also very recently completed phase IIb clinical trials. [11][12][13] For example, rhodium complexes of ferroquine display moderate activity when evaluated in vitro. Many analogues of ferroquine have since been reported.…”