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Effect of a methylenedioxy-flavonoid isolated from iresine diffusa on the cellular viability of leishmania mexicana and the intracellular homeostasis of Ca<sup>2+</sup>

Abstract:

The hemoflagellate parasite Leishmania is the cause of leishmaniasis, which depending on the infecting species, can generate three clinical patterns: cutaneous, mucocutaneous or visceral leishmaniasis. This parasitosis is one of the most neglected tropical diseases group in the world and mainly affects the poorest countries. Current treatment for this disease is based on the use of pentavalent antimonials (Glucantime® and Pentostam®) as well as other second-line drugs. However, these drugs have toxic effects for patients and frequently the parasite shows resistance. In this sense, several investigators have oriented their efforts to study new drugs as an alternative for the cure of this disease, carrying out research with several compounds of natural origin, in order to achieve a parasiticidal action with low toxicity in humans. In this work, we aimed to study the effect of 5-methoxy, 6,7-methylenedioxy-flavone (Flavonoid 1), isolated from Iresine diffusa (known as Valerian in our country), on Leishmania mexicana. We obtained an inhibitory effect on cell proliferation and decreased percentage of macrophages infected with amastigotes of L. mexicana (IC50 = 1.47 μM), also observing alteration on the intracellular Ca2+ concentration. Similarly, Flavonoid 1 has a rapid and total effect on the dissipation of the mitochondrial electrochemical potential, as well as a direct effect on the alkalinization of the acidocalcisomes on the promastigotes of these parasites. The results suggest that the chemically modified compound could be the basis of a future treatment against this disease.