Trojan horse effect

ZLOTKIN, A., CHILMONCZYK, S., EYNGOR, M., HURVITZ, A., GHITTINO, C. ELDAR, A. (2003) Trojan horse effect phagocyte-mediated Streptococcus iniae infection of fish. Infection and Immunity, 71,2318. 

In effect, antimalarial trojan horse drugs of this type should deliver a double blow to the parasite by exploiting the presence of high concentrations of ferrous ion present in the parasite food vacuole as the trigger for protease inhibitor release. In model studies with prototype 81d, in the presence of ferrous ions, these systems readily degrade to produce the desired chalcone (82b, R = H, in 45% yield from 81d), in tandem with secondary carbon-centred radical 82a (Scheme 29). Furthermore, analogues 81d-f have superior in vitro antimalarial activity to that of arteflene (<25 nM in vitro versus Plasmodium falciparum, arteflene >50 nM). The other product obtained is the diol (82c), a product of two-electron reduction of the endoperoxide bridge. 

It was thus shown for the first time, that GSH adducts of STL possess their own biological activity and may thus be involved in the overall effects observed after administration of STL. They should thus not be considered mere deactivation products. Although the adducts did not show any inhibitiory activity in experiments with glutathione reductase and glyoxalase [41], it can be expected that further enzymes involved in GSH metabolism will be affected by such adducts in a similar manner. STL-GSH adducts might thus even be considered as Trojan horses that can bring the STL molecules close to active centers of certain enzymes with GSH binding sites. 

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