engleski

In vitro determination of antileishmanial activity of 3, 4-ethylenedioxythiophene

Leishmaniasis is a disease caused by over 20 species of protozoan Leishmania parasites and is transmitted to humans by the bite of infected female Phlebotomine sand flies. It is one of the world’s most neglected diseases affecting 12 million people in 98 countries, with 350 million people considered at risk of infection and 40.000 deaths per year. Current leishmaniasis treatment relies exclusively on chemotherapeutic drugs, such as pentavalent antimonials, amphotericin B, miltefosine, and paromomycin. These drugs have a limited efficacy due to growing resistance, frequent side effects and high cost of treatment. Pentamidine, which was serving as template in designing of diamidine compounds, is currently a second-line drug in visceral leishmaniasis treatment. The aim of this study was to determine antileishmanial activity of three diamidine derivatives of 3, 4-ethylenedioxythiophene (M1-M3) on Leishmania infantum promastigotes. Different amounts of diamidine derivatives were added in tubes with Leishmania infantum promastigotes and incubated at 25°C/48. Inhibition growth (IG50) was determined by counting the promastigotes in hemocytometer chamber (Neubauer chamber) and comparing with negative (untreated) control. Biological results showed that these compounds displayed lower inhibitory concentrations against L. infantum than pentamidine. In biophysical experiments tested diamidine derivatives showed selective binding to DNA over RNA. Additional experiments showed that compounds exhibit strong affinity toward AT base pair but they also bind to GC base pair. It is well known that pentamidine and other related diamidines bind specifically to AT minor groove sequences in DNA, and based on the obtained biophysical results it can be assumed that DNA binding could be involved in the mechanism of action of the tested diamidines.

Leishmania infantum; activity; in vitro; diamidines; DNA

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