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

• Published in: Medicinal chemistry research Vol. 32; no. 1; pp. 158 - 164
• Main Authors: Seck, Insa, Ciss, Ismaïla, Diédhiou, Adama, Baldé, Mamadou, Ka, Seydou, Ba, Lalla A., Ndoye, Samba F., Figadère, Bruno, Seon-Meniel, Blandine, Gomez, Generosa, Cojean, Sandrine, Pomel, Sébastien, Loiseau, Philippe M., Fall, Yagamare, Seck, Matar
• Format: Journal Article
• Language: English
• Published: New York Springer US 2023; Springer Nature B.V; Springer Verlag
• Subjects: Antiparasitic agents; Antiprotozoal agents; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Chemical compounds; Chemical Sciences; Cholesterol; Drug resistance; Drugs; Germfree; Inorganic Chemistry; Leishmania donovani; Leishmaniasis; Life Sciences; Malaria; Medicinal Chemistry; Microbiology and Parasitology; Morbidity; Original Research; Parasitology; Pharmacology; Pharmacology/Toxicology; Plasmodium falciparum; Populations; Protozoa; Selectivity; Triazoles; Tropical diseases; Trypanosoma brucei gambiense; Trypanosomiasis; Antiparasitic activity; 1,2,3-triazene; Leishmaniasis; Malaria; Trypanosomiasis; 1,2,3-triazole; trypanosomiasis; antiparasitic activity; 1-2-3-triazole; leishmaniasis; malaria; 1-2-3-triazene
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-022-02994-9

Trypanosomiasis, leishmaniasis, and malaria are tropical diseases that affect poor populations and the commonly-used drugs are toxic and can be subject to drug resistance. There is, therefore, an urgent need to find effective therapeutic agents accessible to these populations that bear the brunt of morbidity and mortality. In vitro activities of seven 1,2,3-triazenes ( 1a , 1b , 2a , 2b , 3a , 3b , and 4 ) and five 1,2,3-triazoles ( 5a , 5b , 6a , 6b , and 7 ) were evaluated against Trypanosoma brucei gambiense , Leishmania donovani , and Plasmodium falciparum . The 1,2,3-triazenes showed better activities than 1,2,3-triazoles against Leishmania donovani : 2b was the most effective against axenic amastigote forms of Leishmania donovani LV9 (IC 50  = 0.89 ± 0.41 μM) and the intramacrophage-amastigote forms (IC 50  = 0.99 ± 0.36 μM) with a selectivity index >100. The best trypanocidal activities against Trypanosoma brucei gambiense was observed with the 1,2,3-triazene 3a ( IC 50  = 3.45 ± 0.09 μM) and the triazole 7 , an analog of the cholesterol side chain (IC 50  = 3.99 ± 0.23 μM). The most interesting result against Plasmodium falciparum 3D7 strain was obtained with 5b (IC 50  = 1.29 ± 0.15 μM) with a selectivity index >77. This study revealed that 1,2,3-triazenes and 1,2,3-triazoles show antiparasitic potential that could lead to a new class of drugs. Graphical abstract