1,2,3-triazenes and 1,2,3-triazoles as antileishmanial, antitrypanosomal, and antiplasmodial agents

Abstract

Trypanosomiasis, leishmaniasis and malaria are tropical diseases that affect poor populations and the classical drugs are toxic and select drug resistance. There is, therefore, an urgent need to find effective therapeutic agents accessible to developing countries that bear the brunt of morbidity and mortality.In this study, we evaluated the in vitro activities of fourteen 1,2,3-triazenes and 1,2,3triazoles against Trypanosoma brucei gambiense, Leishmania donovani and Plasmodium falciparum. Moreover, the synthesis of two new products among them will be described.The 1,4-disubstituted 1,2,3-triazenes showed better activities than 1,2,3-triazoles against Leishmania donovani with selectivity indexes greater than 100. Thus, compound 2b was the most effective one against axenic amastigote forms of Leishmania donovani LV9 with an IC 50 of 0.89 ± 0.41 M, and against the intramacrophagic amastigote forms, with an IC 50 value at 0.99 ± 0.36 M.Compounds 3a, a 1,2,3-triazene and 8, a triazole analogue of the cholesterol side chain, showed the best trypanocidal activities against Trypanosoma brucei gambiense with IC 50 of 3.45 ± 0.09 M and 3.99 ± 0.23 M, respectively.The most interesting result against the Plasmodium falciparum 3D7 strain was obtained with 5b with an IC 50 value of 1.29 ± 0.15 M.The present study revealed that 1,2,3-triazenes and 1,4-disubstituted 1,2,3-triazoles are chemical entities exhibiting an antiparasite potential that could lead to a new class of drug candidates.

Novel Benzotriazole‐β‐lactam Derivatives as Antimalarial Agents: Design, Synthesis, Biological Evaluation and Molecular Docking Studies

“…Considering malaria's still high prevalence and mortality rates, as well as drug resistance to known antimalarials, new and effective drugs are urgently needed. [8] The widely demonstrated importance of the biological properties of heterocyclic compounds has led organic chemists to develop efficient methods for synthesizing many derivatives for testing and pharmaceutical development. [9] Standing out prominently among these are 2-azetidinones (β-lactams), which constitute an important class of compounds, especially due to their biological activities [10][11][12][13][14][15] as antimicrobial, [16][17][18][19] antifungal, [20] antimalarial, [5,21] anti-inflammatory, [17,22] and anticancer [19,[23][24][25] agents.…”

“…Even though medicines successfully treated malaria, resistance is a serious issue. Considering malaria‘s still high prevalence and mortality rates, as well as drug resistance to known antimalarials, new and effective drugs are urgently needed [8] …”