Compounds for the treatment of Leishmaniasis and other diseases caused by trypanosomes.

Researchers from the University of Granada and the University of Valencia have observed antiparasitic activity in a series of aromatic heterocyclic compounds, thus enabling their use as a treatment against diseases caused by protozoa of the Trypanosomatidae family, mainly Leishmaniasis, and within these, visceral Leishmaniasis, cutaneous Leishmaniasis or mucocutaneous Leishmaniasis.

Leishmaniasis is an infectious and parasitic disease, classified as a “neglected tropical disease” by the WHO, which affects millions of people every year and exists mainly in developing countries. Despite its relevance and incidence, there is still no effective vaccine or effective treatment to combat it. The drugs currently used have some disadvantages such as high toxicity, difficulty in administration, generation of resistance, and high cost. The global set of these problems, also common to other diseases caused by parasites of the Trypanosomatidae family, such as Chagas disease, imply the need for the development of new, more effective treatments that represent an alternative to the usual ones.

Compounds proposed in this invention are a group of aromatic heterocycles linked to simple acyclic polyamines that have shown antiparasitic activity against three strains of the genus Leishmania that are the main causes of Leishmaniasis.

It has been shown that the survival of parasites of the Trypanosomatidae family is closely linked to the activity of its enzyme superoxide dismutase (FeSOD), which plays a relevant role in the development of Chagas disease or Leishmaniasis. The compounds proposed as a treatment in this invention cause the parasite to be affected without actually causing a relevant inhibition of the human enzyme. This is because such compounds show an inhibition capacity of the FeSOD enzyme of the parasite with IC50 values lower than the IC50 value necessary to significantly inhibit the human erythrocyte enzyme.

Moreover, according to the results of the assays carried out, these compounds have lower toxicity than the toxicity associated with the use of the reference commercial treatments.

ADVANTAGES AND BENEFITS

Greater antiparasitic activity. The antiparasitic activity against the Leishmania strains tested is, in almost all of the proposed compounds, higher than said activity performed by the reference commercial treatment.

Low toxicity. Current commercial treatments to combat these diseases are highly toxic. These compounds show lower toxicity than that observed in them.

Affection of the parasite without inhibiting the human enzyme. The compounds of the invention can inhibit the parasite FeSOD enzyme with an IC50 value lower than that necessary to significantly inhibit the human erythrocyte enzyme.

Possibility of industrial scaling. Due to the simplicity of the proposed synthesis method and the ease of scaling it for industrial production.