AI Article Synopsis
- Pyrimethamine, an antimalarial drug, also inhibits crucial enzymes in the leishmanial folate pathway, but requires high concentrations for effectiveness in living organisms.
- Targeted drug formulations, CMD-P and SD-P, were developed to deliver pyrimethamine directly to leishmanial parasites within macrophage cells.
- CMD-P showed promising results by eliminating about 50% of amastigotes with minimal toxicity to host cells, while SD-P was less effective, highlighting the potential for safer leishmaniasis treatments using targeted drug delivery.
Article Abstract
Pyrimethamine, an antimalarial drug, was found to be able to inhibit both enzymes (DHFR-TS and PTR1) of the leishmanial folate pathway, although this effect in vivo appears only in relatively high concentrations. To reach the parasites inside macrophage cells, where they are sheltered, targeted drugs of pyrimethamine, carboxymethyldextran-thiomannopyranoside-pyrimethamine (CMD-P), and succinyldextran-thiomannopyranoside-pyrimethamine (SD-P), were synthesized and assayed against L.(L.) amazonensis amastigotes. CMD-P has 2.43% and SD-P has 2.58% of pyrimethamine attached. At a CMD-P dose of 200 microg/mL (4.86 microg/mL pyrimethamine), the results were very promising, with a destruction of approximately 50% of the intracellular amastigotes, with no detectable toxicity to macrophage cells. SD-P in similar doses did not show good results, probably due to different patterns of drug release. These results open the possibility of treating leishmaniasis with a safe targeted drug of pyrimethamine released directly inside the macrophage cells, reducing the host systemic toxicity.
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