Metal-Based Drugs for Treatment of Malaria

Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents

“…The activity of platinum complexes goes as far back as the 1960s with the epochal discovery of the anticancer activity of cis-diamminedichloridoplatinum(II), commonly known as cisplatin, by Rosenberg and co-workers [73]. Next generation platinum(II) derivatives (77)(78)(79), shown in Figure 20, have since been developed and approved to address the challenges faced by cisplatin (76), namely, limited selectivity, development of clinical resistance, and acute toxicity [74,75]. Numerous examples of inorganic platinum complexes possessing antiplasmodial activity have been reported in the literature.…”

“…Numerous examples of inorganic platinum complexes possessing antiplasmodial activity have been reported in the literature. Several reviews [ 19 , 76 , 77 ] and a published book chapter [ 78 ] give detailed accounts of antiplasmodial platinum-based complexes. Representative examples of inorganic platinum complexes 80 – 81 with antimalarial activity are also illustrated in Figure 21 [ 20 , 79 ].…”

A quantum mechanics and molecular mechanics study of bis-thiosemicarbazones with strong antiplasmodial properties as Fe(iii)-selective chelators and inhibitors of hemozoin formation

“…Antimalarial drugs exert their therapeutic effects through different mechanisms, including the prevention of endogenous iron uptake by plasmodium parasites and inhibition of b-hematin (bHM) formation within the parasitic cells. 5,7 Hemoglobin catabolism in the host's red blood cells by plasmodium parasites releases iron(III) protoporphyrin IX [Fe(III)PPIX], also called free heme, as a by-product that is highly cytotoxic. To prevent cell damage or death, malaria parasites detoxify free heme via biomineralization into a harmless substance called hemozoin that is chemically and structurally identical to bHM, its synthetic counterpart.…”

Facing Diseases Caused by Trypanosomatid Parasites: Rational Design of Pd and Pt Complexes With Bioactive Ligands

“…In the last decades, the development of metal-based drugs has proven to be a promising approach in the search for new therapeutic tools against parasitic diseases. As a result of the research performed by several academic groups, a great number of classical coordination compounds and organometallics bearing antiparasitic activity were developed (Sánchez-Delgado et al, 2004;Navarro, 2009;Navarro et al, 2010;Gambino, 2011;Gambino and Otero, 2012;Salas et al, 2013;Tahghighi, 2014;Brown and Hyland, 2015;Pessoa et al, 2015;Camarada et al, 2016;Gambino and Otero, 2018;Marcelino et al, 2018;Ravera et al, 2018;Gambino and Otero, 2019;Markwalter et al, 2019;Ong et al, 2019;Mbaba et al, 2020;Păunescu et al, 2021).…”