Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological

Abstract

Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which could be used for the pharmacological control of Chagas disease, leishmaniasis, and African trypanosomiasis.

Keywords: African trypanosomiasis; Chagas disease; DETC; Trypanosomatids; antiparasitic activity; dithiocarbamates; leishmaniasis.

Figure 1

Schematic representation of the chemical synthesis of dithiocarbamates-based compounds.

Figure 2

Compounds based on dithiocarbamate used as potential anti-Trypanosoma cruzi drugs. The figure represents the different structures of dithiocarbamates that showed antiparasitic activity. These compounds showed antiparasitic activity at a concentration of 5 µM during 72 h of treatment against the T. cruzi parasite. Increased production of reactive oxygen species seems to be the probable mechanism of action for these compounds to exhibit antiparasitic activity [26].

Figure 3

Thiadiazine-based synthetic compounds bound to dithiocarbamates with activity against Trypanosoma cruzi. The different substituents, represented by R1 and R2, may be attached to circular structures formed by thiadiazine and dithiocarbamate. The biological activity of these molecules appears to be related to their ability to inhibit the cysteine protease enzyme and increase oxidative damage in T. cruzi [31].

Figure 4

Chemical compounds synthesized from tryptophan with dithiocarbamates used as antiparasitic drugs against Leishmania donovani and Trypanosoma cruzi. In this figure is possible that different substituents (R: H or OMe) interact with the structure formed for tryptophan-dithiocarbamate. These structures are more efficient in inducing mitochondrial damage and consequently parasite death [47].

Figure 5

Sodium diethyldithiocarbamate (DETC) three-dimensional (3-D) chemical structure used as a potential anti-Leishmania sp. drug. DETC acts as a metal chelator and therefore inactivates enzymes essential for parasite survival [49,50].

Figure 6

Synthetic dithiocarbamate derivatives bound to metal centres used as potential anti-Leishmania sp. drugs [52]. Two distinct chemical structures (A and B) that when interacting with metals (Mn²⁺ or Zn²⁺) exhibit enhanced antiparasitic activity against L. donovani parasites.

Figure 7

Synthetic dithiocarbamate derivatives bound to thiadiazone used as potential anti-Trypanosoma brucei rhodesiense drugs. The basic structures may receive different chemical substituents (R and R‘) that could influence the antiparasitic activity of the new synthesized compounds [62].

Figure 8

Synthetic dithiocarbamate derivatives bound to gold used as potential antiparasitic drugs against Trypanosoma brucei, Leishmania infantum, Trypanosoma cruzi and Plasmodium falciparum. The main biological activity attributed to this structure is related to its ability to induce oxidative stress and consequently parasite death [65].