Antiprotozoal Agents

Heavy metal drugs are effective antiprotozoal agents.

For example, sodium stibogluconate, or SSG, contains the heavy metal antimony and is widely used to treat Leishmania infections.

In the host, Leishmania lives inside macrophages.

Once administered, the drug enters the macrophages and then enters the parasite through aquaglyceroporin channels.

Thiol systems inside the parasite and the macrophages change SSG’s pentavalent antimony into the active trivalent form.

This active form blocks the enzyme trypanothione reductase, disrupting the parasite’s redox system.

Trivalent antimony also binds to free thiols and interferes with iron-sulfur cluster enzymes and zinc-binding proteases.

As a result, reactive oxygen species accumulate within the cell, damaging its proteins and membrane lipids.

The active drug then promotes the efflux of intracellular thiols, further weakening the parasite’s defense.

These effects ultimately result in the death of Leishmania and their removal from the host’s body.