**Acknowledgements**

burden of the spleen and liver, indicating that this compound is a potential drug against

TiO2@Ag nanoparticles (TiAg-Nps) produce reactive oxygen species (ROS), which have an antimicrobial effect, including antileishmanial effects on *Leishmania tropica* and *Leishmania infantum* promastigotes and amastigotes, mainly non-visible light-exposed TiAg-Nps [117]. Twenty-four porphyrin precursors and derivatives were evaluated against *Trypanosoma brucei*, *L. donovani*, and *Plasmodium* sp. The perforine 4i derivative showed the best activity against *T. brucei* with a MEC value of 6.25 mM, but the compound was not active against

Another approach used in studies is the combination of drug therapies aimed at finding the most effective and secure one. Pam3Cys (an in-built immunoadjuvant and TLR2 ligand) and miltefosine were combined and the resulting combination was evaluated. All experiments were done in BALB/c mouse. Parasitic inhibition significantly increased in groups treated with combinations of the drugs compared to groups receiving miltefosine and Pam3Cys separately. Moreover, increased production of Th1 cytokines, RNS, ROS, and H2O2, as well as increased

Several aromatic/heterocyclic sulfonamides and 5-mercapto-1,3,4-thiadiazoles were recently investigated against *L. donovani* CAs. The sulfonamides were medium potency-weak inhibi‐ tors, but some heterocyclic thiols inhibited the enzyme with KIs in the range of 13.4–52 nM. Microscopic studies revealed cell swelling and structural alterations on the flagellar pocket such as presence of vacuoles. Autophagic vacuoles that cause intracellular damages and parasite death, and accumulation of intracytoplasmic electron-dense granules were also induced by the inhibitors. These result suggest that β-CA from *Leishmania* is a potential new

Leishmaniasis is a neglected, potentially lethal infectious disease caused by parasites in the genus *Leishmania* that affects many developing countries. Infection can lead to tegumentary or visceral manifestations of the disease. The tegumentary form of leishmaniasis (TL) includes cutaneous, mucocutaneous, and diffuse clinical manifestations, whereas visceral leishmaniasis (VL), or Kala-azar, affects organs and internal tissues. The treatment of VL is challenging and long. Treated patients need monitoring and hospitalization. Therapeutic problems include toxicity and teratogenicity of the available drugs, and low response in human immu‐ nodeficiency virus (HIV)/*Leishmania* co-infections. In addition, drug resistance is increasing. Moreover, leishmaniasis received little attention from governments and the pharmaceutical industry until the last decade. The absence of either prophylactic or preventive vaccine

The development of new parasite targets and synthetic drugs along with the research on natural products represents a major strategy for the discovery of new compounds against

phagocytosis were observed during the study of immunological alterations [119].

visceral leishmaniasis [116].

antileishmanial drug target [102].

candidates makes it further difficult to control the disease.

**7. Conclusions**

Leishmania sp.

intramacrophage amastigotes of *L. donovani* [118].

364 Leishmaniasis - Trends in Epidemiology, Diagnosis and Treatment

This study was supported by grants from Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (MCT/ CNPq), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and Fundação Oswaldo Cruz (FIOCRUZ). The authors are grateful to Iêda Coleto Miguel de Castro and Silvia Rocha de Souza for technical support.
