In Vitro Evaluation of Esters of Quinoxaline-1,4-di-N-oxide Derivatives as New Antitaeniasis Agents and Their Inhibitory Activity Against Triosephosphate Isomerase.

Background/

Objectives

Pork tapeworm Taenia solium is the causative agent of cysticercosis which may develop in muscle tissue, skin, eyes, and the central nervous system (neurocysticercosis). It is estimated by the World Health Organization (WHO) that about 2.56-8.30 million are infected worldwide. Praziquantel and albendazole are used for anthelminthic treatment of neurocysticercosis; however, not all patients have a complete elimination of cysts, which makes it necessary to seek new and improved treatment options.

Methods

In this study, methyl, ethyl, n-propyl, and iso-propyl quinoxaline-7-carboxylate-1,4-di-N-oxide derivatives were evaluated in vitro against Taenia crassiceps (T. crassiceps) cysts. Additionally, to know their potential mode of action, a molecular docking analysis on T. solium triosephosphate isomerase (TsTIM) and an enzyme inactivation assay on recombinant TsTIM were carried out.

Results

Nine compounds had time- and concentration-dependent cysticidal activity. Particularly, compounds TS-12, TS-19, and TS-20 (EC50 values 0.58, 1.02, and 0.80 µM, respectively) were equipotent to albendazole sulfoxide (EC50 = 0.68 µM). However, TS-12 compounds only cause a slight inhibition of TsTIM (<40% at 1000 µM), suggested that another drug target is implicated in the biological effects.

Conclusions

These results demonstrated that quinoxaline 1,4-di-N-oxide is a scaffold to develop new and more potent antitaeniasis agents, although it is necessary to explore other pharmacological targets to understand their mode of action.