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

Abstract

In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria.

Synthesis and Antiparasitic Activity of New Conjugates—Organic Drugs Tethered to Trithiolato-Bridged Dinuclear Ruthenium(II)–Arene Complexes

“…The ruthenium(II)-arene organometallic scaffold proved to be a versatile platform for the design of novel bioorganometallic agents and cationic or neutral compounds with the general structure [(η 6 -arene)Ru(X)(Y)(Z)] presenting both hydrophobic and hydrophilic properties have attracted increasing attention [14]. Following the work pioneered by RAPTA-C and RM175, studies on organometal-Inorganics 2021, 9, 59 2 of 25 lic ruthenium(II)-arene complexes are not only rapidly progressing but also particularly relevant, with a plethora of compounds presenting anticancer, antibiotic, antifungal and antiparasitic properties [15][16][17][18][19][20]. Important research focused on hybrid structures in which the robust ruthenium(II)-arene unit is associated with the various biologically active compounds, a strategy with implications for developing of novel metal-based compounds presenting multiple targets [21].…”

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).…”

Trithiolato-Bridged Dinuclear Arene Ruthenium(ll)- Glycoconjugates: Synthesis and Antiparasitic Activity

“…As the use of platinumbased drugs is limited due to shortcomings as the occurrence of chemoresistance and side effects associated to their high toxicity [4,5], this encouraged the research of compounds based on other metals as alternative to platinum anticancer therapeutics [1,6] , [7,8]. Parallel investigations aimed to enlarge the purpose of metal complexes with the identification of additional pharmacological properties, such as antibiotic [9,10] and antiparasitic [11][12][13][14][15][16].…”

“…Organometallic complexes based of the ruthenium(II)-arene scaffold constitute an important direction of study. Pioneered by RAPTA-C [19] (Ru(II)[(η 6 -p-MeC6H4Pr i )(PTA)(Cl)2] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1]decane)) and RM175 [20] ([Ru(II)(η 6 -C6H5-C6H5)(en)Cl] + (en = ethylenediamine)) complexes, the Ru(II)-arene moiety has been used in a myriad of compounds to improve anticancer activity and selectivity [21][22][23][24][25], but also for other therapeutic applications [11,13,16,26].…”