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

Abstract

Human African Trypanosomiasis (HAT), Chagas disease or American Trypanosomiasis (CD), and leishmaniases are protozoan infections produced by trypanosomatid parasites belonging to the kinetoplastid order and they constitute an urgent global health problem. In fact, there is an urgent need of more efficient and less toxic chemotherapy for these diseases. Medicinal inorganic chemistry currently offers an attractive option for the rational design of new drugs and, in particular, antiparasitic ones. In this sense, one of the main strategies for the design of metal-based antiparasitic compounds has been the coordination of an organic ligand with known or potential biological activity, to a metal centre or an organometallic core. Classical metal coordination complexes or organometallic compounds could be designed as multifunctional agents joining, in a single molecule, different chemical species that could affect different parasitic targets. This review is focused on the rational design of palladium(II) and platinum(II) compounds with bioactive ligands as prospective drugs against trypanosomatid parasites that has been conducted by our group during the last 20 years.

Multifunctional organometallic compounds for the treatment of Chagas disease: Re(i) tricarbonyl compounds with two different bioactive ligands

“…In this context, the rational design of metal-based drugs including different metal ions or organometallic centers has shown to be a successful strategy for the development of new prospective agents against T. cruzi . 11–22…”

“…This approach has led in many cases to multifunctional compounds showing multiple modes of action and, additionally, to reduced toxicity and favorably modified selectivity profile. 11–14…”

“…In this context, the rational design of metal-based drugs including different metal ions or organometallic centers has shown to be a successful strategy for the development of new prospective agents against T. cruzi. [11][12][13][14][15][16][17][18][19][20][21][22] The current working strategy of our group to obtain new metal-based antiparasitic compounds with improved biological profiles is based on the rational design of multifunctional metal compounds through molecular hybridization of different pharmacophoric moieties to produce an hybrid compound. [23][24][25] This design strategy involves the inclusion in a single chemical entity of a bioactive or pharmacologically relevant metal center, a bioactive ligand, i.e.…”

“…This approach has led in many cases to multifunctional compounds showing multiple modes of action and, additionally, to reduced toxicity and favorably modified selectivity profile. [11][12][13][14] In this work, we report on the rational design of multifunctional Re(I) tricarbonyl compounds with two different bioactive ligands as prospective antichagasic agents: a polypyridyl NN derivative of 1,10-phenanthroline and a monodentate azole (Fig. 1).…”

Platinum and Palladium Organometallic Compounds: Disrupting the Ergosterol Pathway in Trypanosoma cruzi

“…In the past years, our group has contributed to demonstrate that the rational design of metal‐based drugs including different metal ions or organometallic centers and bioactive ligands could be a successful strategy for the development of new prospective agents against T. cruzi . In fact, this approach has led in many cases to multifunctional compounds showing multiple modes of action and, additionally, to a favorably modified selectivity profile towards the parasite [5b,6] …”