Metal-based drugs are used to treat a wide range of diseases; for example, platinum derivatives to treat ovarian [1] and lung cancer [2], bismuth derivatives to treat gastric ulcers caused by Helicobacter pylori [3] or lithium to treat bipolar disorders [4]. Thanks to the therapeutic effect of these drugs, progress has been made in the research of new metal-containing compounds, which have shown potential in the management of multiple diseases through different assays [5].

Among the metals that have become of interest to pharmacology is vanadium (V) because, during the last decades, compounds with this metal have shown therapeutic properties that depend on several factors, among them: the type of compound, its oxidation state, the route of administration and the dose used [6]. Multiple ways through which V exerts its activity have been reported, such as: participation in reactions that generate reactive oxygen species (ROS), reactive nitrogen species (RNS) and free radicals [7], [8], [9]. Another way is to cause enzyme inhibition, mainly of some regulatory phosphatases, due to the structural and electronic similarity of the vanadate ion with phosphate [10], and it is also able to interact with lipids, proteins and DNA due to the generation of ROS [11], [12], [13].

Due to the different interactions of this metal, some potential therapeutic uses such as an antineoplastic [14], [15], hypoglycemic [16], [17] antibacterial [18], [19] and as antiparasitic agent could be suggested, because its use represents an innovative and cost-effective approach for the discovery of new metal compounds since they are less expensive and more accessible for the treatment of diseases [6].

The objective of this review is to describe in detail the targets and the mechanism of action of some V compounds with antiparasitic effect on Plasmodium spp., Leishmania spp. and Trypanosoma cruzi.

Parasitic infections are currently a public health problem due to multiple factors that contribute to their high prevalence worldwide, mainly in developing countries [20]. Among parasitic infections, those transmitted by biological vectors such as malaria, leishmaniasis and trypanosomiasis are of great importance since their transmission is reported during all seasons of the year, and they are widely distributed [21].

The increase in the incidence and distribution of these parasitoses is linked to a wide range of epidemiological factors with higher prevalence in areas with predominantly low socioeconomic strata, the resistance of the vectors to insecticides, and the change in their behavior and distribution that is closely related to climate change [21], [22] and mutations in the genome of parasites causing resistance to the multiple drugs used for their control [23], [24]. The latter having the greatest impact on morbidity [21].

Therefore, to overcome the problem of drug resistance, a promising approach in the search for new antiparasitic compounds focuses on the development of bioactive metal complexes; that is, new drugs that incorporate in their structure metals since they have proven to have effective action against some parasites such as: gold complexes [25] ruthenium [26] copper and platinum [27] complexes against Leishmania spp.; gold [25] and ruthenium [27] against Trypanosoma cruzi; as well as silver nanoparticles [28] and platinum nanoparticles [29] against Plasmodium spp. Moreover, among these metal complexes it has been observed that those incorporating V in their chemical structure have a broad spectrum of activity in different parasitosis with multiple targets and different ways of acting (Figure 1), so the introduction of this metal enhances their therapeutic applications. This is the main reason why, in this review, we will focus on V.

Malaria is a disease transmitted by the bite of a female mosquito of the genus Anopheles, the causal parasite is of the genus Plasmodium which belongs to the Phylum Apicomplexa. There are five species that infect humans, P. vivax, P. ovale, P. malariae, P. knowlesi and P. falciparum. The latter is responsible for the highest number of cases and deaths [30]. The World Health Organization reported that in the year 2021 there were 247 million cases, an increase from 245 million in comparison to 2020 and 619 000 deaths. The African region continues to bear the greatest burden of malaria. Globally, in 2021, the region accounted for 95% of all malaria cases (234 million) and 96% of all malaria deaths (593 000) [31].

The pathogenesis of complicated malaria (which largely accounts for multi-organ cell damage and death), mostly by P. falciparum, is related to several virulence mechanisms that cause vascular obstruction such as: a) sequestration and cytoadherence of parasitized erythrocytes to endothelia, which allows late-stage parasites to evade splenic phagocytosis; b) rosette formation by parasitized and non-parasitized erythrocytes plus platelet-mediated clumping; and c) local inflammatory response. Adhesion of infected erythrocytes to cerebral endothelial cells or placental syncytiotrophoblast can lead to severe complications, known as cerebral and placental or maternal malaria, respectively [32]. Malaria patients have increased production of oxidizing agents and reduced antioxidant defenses, which favor oxidative stress [33].

According to recent research, the cytoadherence phenomenon is not restricted to P. falciparum infection because there is evidence that P. vivax also produces cytoadherence events to endothelium and placental tissue, apparently through proteins with variant interspersed repeats (VIR) and has the ability to form rosettes [34] which may cause an increase in cases of complicated malaria.

The treatment of malaria is based on different types of developed drugs: quinolinics, antifolates, artemisinin derivatives and some antibiotics [24]. The drug of choice is chloroquine, a quinolinic derivative; however, resistance of plasmodia to this compound has been reported. In these cases, a combination therapy with artemisinin derivatives is administered, but unfortunately, with the passage of time, cases of resistance to these derivatives have also been reported in areas of Southeast Asia [35].

Leishmaniasis is a disease caused by the protozoan Leishmania spp. transmitted by the bite of phlebotomine sand flies of the genus Phlebotomus and Lutzomyia [36]. This parasitosis is characterized by the manifestation of cutaneous and mucocutaneous lesions and visceral involvement. It is globally distributed and endemic in 102 countries. Annually, 1.3 million new cases and 20 000–30 000 deaths are reported [37], [38].

Cutaneous leishmaniasis is the most common form, manifested by ulcerative skin lesions that leave lifelong scars and are a cause of severe disability. Ninety-five percent of the cases are reported in the Americas, and new cases are estimated to be between 700 000 and 1 million each year [39]. Mucocutaneous leishmaniasis causes partial or total destruction of the mucous membranes of the nose, mouth and throat, which affects the quality of life of people who suffer from it, while visceral leishmaniasis (also known as "kala azar") is the most severe clinical form and in more than 95% of cases is fatal; it is characterized by irregular episodes of fever, weight loss, hepatosplenomegaly and anemia [38], [39].

The treatment of this disease is with pentavalent antimonials, pentamidine, amphotericin B or miltefosine. These are highly toxic and drug resistance has been reported, which makes this disease very difficult to control. Hence, it is important to develop new therapeutic alternatives [23], [40].

American trypanosomiasis, also called Chagas disease, is caused by the protozoan Trypanosoma cruzi, pertaining to family Trypanosomatidae, which is transmitted mainly by contact with the feces of a triatomid insect (also known as kissing bug or vinchuca) that feeds on the blood of humans and animals. The parasite is also transmitted by the congenital route, blood transfusions, infected organ transplants [41], orally and by laboratory accidents [42], [43].

It is estimated that there are between 6 and 7 million people infected worldwide, but the majority of them are concentrated in the 21 endemic areas of Latin America; however, the number of cases has increased in North America, Europe, Africa, in the Eastern Mediterranean and the Western Pacific. This is mainly due to globalization [43] but other aspects such as the modification of agricultural strategies and climate change also play a role in the spread of the disease [44].

The clinical course of Chagas disease usually comprises two phases, the acute and the chronic. The acute phase can last from 4 to 8 weeks, in which the parasites are identified in the blood, but with the passage of time the parasitemia decreases substantially. Acute infection can be asymptomatic or cause a picture that manifests fever, lymphadenitis, inoculation chagoma and bipalpebral edema. The acute phase usually resolves after time; but if infected people are not treated, they will enter intothe chronic phase [43], [44]. In the asymptomatic chronic stage, parasites are not seen in blood smears because they are hidden in cardiac muscle cells or in the gastrointestinal tract. Around 20–30% of infected people will present cardiac problems and 10% digestive, neurological or combined disorders [41], [43].

For the treatment of the disease, drugs developed 50 years ago such as benzimidazole and nifurtimox continue to be used. These are effective when administered at the beginning of the infection, but as the time of the infection elapses, their efficiency decreases, coupled with that the safety profile is low due to the multiple adverse effects observed [43], [44]. Therefore, it is necessary to develop new compounds that have the potential to treat Chagas disease.