**2.3 Inosine-uridine (IU) nucleoside hydrolase (IU-NH, EC:3.2.2.2)**

The nucleoside hydrolase enzyme is an important target for the development of antiparasitic drugs due to its role in the purine salvage pathway. The amino acid sequence and X-ray structure of the enzyme from *L. major* were revealed in 1999 [39]. IU-NH enzyme establishes a homolog in *Leishmania* species.

In contrast to these facts, there is no study on IU-NH enzyme inhibitors possessing *in vitro/in vivo* antileishmanial activity up to our knowledge. Yet, few inhibitors of *Leishmania* IU-nucleoside hydrolase were reported.

Fuernaux et al. reported transition state analogs of nucleosides with IU-NH inhibitory activity [40]. Later, Berg et al. reported iminoribitol derivatives and evaluated their not only *Tabanus vivax*-NH activity but also human purine nucleoside phosphorylase to determine selectivity [41]. In other studies, two ribosequinolone derivatives were tested against *Ld*NH [42] and Casanova et al. reported proanthocyanidins with *Ld*NH activity [43].

### **2.4 Enzymes Involved in Polyamine metabolism in** *Leishmania*

In *Leishmania* parasites (and other members of the trypanosomatids), polyamine pathways can be considered as a unique pathway; most enzymes are essential for parasitic survival and infectivity (**Figure 4**).
