## 5 Summary of Drug Targets Related to Prenylquinone Biosynthesis and Functions  
Phenylquinones are molecules involved in essential metabolic reactions in all organisms, for example, prevention of lipoperoxidation, mitochondrial respiratory chain or as enzymatic cofactors. Surprisingly, only few studies involving prenylquinones as drug targets have been conducted so far, most of them about UQ-related metabolism [41; 54]. The study of these pathways is interesting for the discovery of new drug targets. Moreover, the biosynthesis of prenylquinone precursors should be also considered as interesting metabolic targets for exploration. An important fact is that the aromatic and isoprenic precursors of the prenylquinones were more studied then their specific biosynthesis pathways. In fact, biosynthesis inhibition studies have only been performed in vitro fortocopherol (in _L. amazonensis_ and _Plasmodium falciparum_) and MQ (also in the apicomplexan parasite) [62; 64]. Several compounds known to interfere on shikimate pathway and aminoacid degradation as well as the different pathways for isoprenoid biosynthesis or isoprenic chain elongation have been demonstrated to possess antiparasitic activity. In regard to the aromatic precursor formation in parasitic protozoa, tyrosine degradation has been demonstrated to be essential in _Leishman_ and those enzymatic inhibitors of tyrosine degradation andtocopherol biosynthesis affects _Leishmania proliferation_ and _P. falciparum_[62; 63; 64; 89]. Unlike _Trypanosomatidae_ species, _Apicomplexa_ pathogens seems to require the shikimate pathway for the synthesis of aromatic precursors and corroborating this statement, glyphosate and shikimic acid analogs demonstrated effect against apicomplexan pathogens however there is an evidence that the last enzyme of shikimate pathway is not essential for the _P. berghei_ viability [73]. Regarding to the isoprenic precursor formation in parasitic protozoa drug targets are concentrated in MEP and MVA pathways. First of all, it was previously demonstrated that _G. lamblia_ is sensitive to the statins mevastatin and mevinolin, two classical inhibitors of the MVA pathway and for consequence the isoprenic precursors synthesis [69; 106]. In the case of _Blackocystis_, _Acanthamoeba_ and some apicomplexan parasites, including _Toxoplasma_, _Cryptosporidium_ and _Plasmodium_, it was demonstrated the susceptibility to several other statins and there is an evidence of enzymatic capacity to metabolize MVA in _P. falciparum_ extracts [107; 108; 109; 77; 81; 84]. Curiously, there is no evidence for pathways responsible for isoprenic chain biosynthesis in _E. histolytica_. After the identification of MEP pathway in apicomplexan parasites a vast number of researchers concentrated their efforts around the compound fosmidomycin and analogs. Fosmidomycin is a specific inhibitor of the DXR (1-deoxy-d-xylulose-5-phosphate reductio isomerase) enzyme [79; 80; 109; 110; 111; 112; 113]. Several studies demonstrated the effect of Fosmidomycin on _Plasmodium_ spp., _Babesia_ spp. and _Theileria_ spp. proliferation, however fosmidomycin has a poor effect on _Toxoplasma_, _Theileria_ and _Eimeria_ viability although the MEP pathway is a proven isoprenoid source for apicomplexan parasites, [109; 110; 111; 112]. The elongation of isoprenoid chain is also a promisor chemotherapeutic target against parasitic protozoa. For example, in trypanosomatids and apicomplexan parasites the risedronate and its analogs have shown to be effective FPP/GGPP synthase inhibitors [121; 122; 123; 124; 125; 126]. Also, nerolidol or farnesol (terpenes of essential oils), appear to have growth inhibitory activity in different species, including apicomplexan and trypanosomatid parasites probably because of their structural similarity with the substrates of enlongation pathway enzymes [127; 128; 129; 130; 131]. Another important therapeutic target related to prerylquinones that can be cited is the effect of hydroxynaphtoquinones in parasitic protozoa [160].