Ruthenium Metallotherapeutics: Novel Approaches to Combatting Parasitic Infections

Abstract

Human parasitic infections cause a combined global mortality rate of over one million people per annum and represent some of the most challenging diseases for medical intervention. Current chemotherapeutic strategies often require prolonged treatment, coupled with subsequent drug-induced cytotoxic morbidity to the host, while resistance generation is also a major concern. Metals have been used extensively throughout the history of medicine, with more recent applications as anticancer and antimicrobial agents. Ruthenium metallotherapeutic antiparasitic agents are highly effective at targeting a range of key parasites, including the causative agents of malaria, trypanosomiasis, leishmaniasis, amoebiasis, toxoplasmosis and other orphan diseases, while demonstrating lower cytotoxicity profiles than current treatment strategies. Generally, such compounds also demonstrate activity against multiple cellular target sites within parasites, including inhibition of enzyme function, cell membrane perturbation, and alterations to metabolic pathways, therefore reducing the opportunity for resistance generation. This review provides a comprehensive and subjective analysis of the rapidly developing area of ruthenium metal-based antiparasitic chemotherapeutics, in the context of rational drug design and potential clinical approaches to combatting human parasitic infections.

Antiviral and antimicrobial applications of chalcones and their derivatives: From nature to greener synthesis

“…Due to the lack of a vaccine and the challenges associated with establishing a vector control system, existing antiparasitic management strategies have centered on chemotherapy procedures. The demand for novel pharmacological approaches for managing parasitic disorders stems from a variety of issues, such as the scarcity of medications available, their decreased efficacy owing to microbial resistance, prolonged therapies, and substantial toxicity [ 155 ]. As a result, continuous research into biologically active chemicals to combat these pathogens remains critical.…”

Ruthenium Complexes, an Emerging Class of Leishmanicidal Drug Candidates

“…Ruthenium, a transition metal belonging to group 8 of the periodic table, same as iron, has the ability to interfere with some of the biological processes developed for handling iron in vivo, including transport, cell uptake, and metabolism. Ruthenium complexes are an emerging class of metallopharmaceuticals for the treatment of parasitic infections [30,31]. Indeed, they gather a quite unique set of properties that makes them the best drug candidates for the treatment of leishmaniasis (Figure 1):…”