## 5 Leishmanases  
Diseases that are caused by protozoan parasites from the genus _Leishmania_ (including more than 20 _Leishmania_ species) are called leishmaniasis. These parasites are transmitted to humans through bites by infected female phlebotomine sandflies, tiny (2-3 mm) long insect vectors [6]. Mucocutaneous (MCL), cutaneous (CL), and visceral leishmaniasis (VL) are the three main forms of this disease. As most infected people do not develop disease symptoms, leishmaniasis should refer to the term of becoming sick owing to _Leishmania_ infection without being infected with the parasite [6]. Today, more than 1 billion people living in areas endemic for leishmaniasis are at risk of infection. There are estimates pointing out 30,000 new cases of VL and more than 1 million new cases of CL annually [6]. In cutaneous leishmaniasisis, exposed parts of the body, such as the arms, legs, and face, are affected by ulcers that produce many lesions that cause serious disability. Mainly seen in the Eastern hemisphere, Old World cutaneous leishmaniasisis is caused by _L. infantum_, _L. donovani_, _L. ethiopica_, _L. tropica_, and _L. major_, whereas New World cutaneous leishmaniasis (prevalent in Central and South America) is predominantly caused by _L. amazonensis_, _L. braziliensis_, _L. guyanensis_, _L. panamensis_, _L. Mexicana_, and _L. peruviana_[24]. In the case of mucocutaneous leishmaniasisis, the mucous membranes of the mouth, nose, and throat cavities are affected. In visceral leishmaniasisis, symptoms such as anemia, fever, weight loss, and swelling of the spleen and liver are observed [6]. Currently used antileishman treatments include pentavalent antimonials [25], amphotericin B [26], miltefosine [27], paromomycin [28], and topical and systemic azoles [29]. It is difficult to deliver a complete cure for all forms of leishmaniasisis, including CL, ML, and VL. Consequently, there is a tchance of relapse as the parasite remains in the body of the host. To complete their life cycle, the _Leishmania_ parasites encompass vertebrate (animal with spinal cords) and invertebrate (spineless animals) host species, as well as two developmental forms (pro-mastigotes and amastigotesited in the sand flies and mammalian hosts, respectively) [30]. Early diagnosis and effective and prompt treatment reduce the prevalence of the disease and prevent disabilities and death. Vector control helps to interrupt or reduce the transmission of disease by reducing the number of sandflies. Control measures include the use of insecticide-treated nets, insecticide spray, environmental management, and personal protection [6]. Squalene Synthase and Farnesyl Diphosphate Synthase: Targets for Anti-_Tympanosidase_ Drug Discovery  
Squalene synthase is an enzyme that catalyzes the first reaction of the branch of the isoprenoid metabolic pathway committed specifically to sterol biosynthesis [31]. In _Leishmania_ parasites, the dimerization of two farnesyl pyrophosphate molecules to produce squalene is catalyzed by squalene synthase. Next, squalene undergoes a number of enzymatic reaction steps to yield ergosterol, in contrast to cholesterol in humans [32]. The basic structure of sterol molecules (such as cholesterol, ergosterol, etc.) is derived from acetyl-CoA through the mexolonate pathway (Figure 2) [33]. In the mexolonate pathway, there is condensation of two acetyl-CoA units to afford acetoacetyl-CoA in the presence of acetoacetyl-CoA thiolase (a cytosolic enzyme). This reaction is followed by the addition of a third acetyl-CoA unit to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA), which is then reduced by NADPH to give mexolonic acid by using two mitochondrial enzymes in trypanosomatids, i.e., HMG-CoA synthase and HMG-CoA reductase, respectively [34]. In humans, the enzymes involved in the mevalonate pathways have been reported to occur in the cytosol and endoplasmic reticulum, especially in peroxisomes and glycosomes [33].