Synthesis and in vitro antileishmanial activity of alkylene-linked nitrofurantoin-triazole hybrids

• DOI: 10.1016/j.ejmech.2022.115012
• Publication Date: 2022-12-07T16:41:00Z
• Authors: Nonkululeko H. Zuma; Janine Aucamp; Helena D. Janse v...; David D. N'Da
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Nitrofurantoin; Antiprotozoal Agents; Humans; Leishmaniasis, Visceral; Leishmaniasis; Leishmania donovani; 3. Good health

Leishmaniasis is a vector-borne parasitic disease that mostly affects populations in tropical and sub-tropical countries. There is currently no protective anti-leishmanial vaccine and only a paucity of clinical drugs is available to treat this disease albeit their toxicity. Leishmaniasis is curable but its eradication and elimination have been hampered by the emergence of multidrug resistant strains of the causative pathogens. This heightens the necessity for new and effective antileishmanial drugs. In search for such agents, nitrofurantoin, a clinical antibiotic, was appended to triazole scaffold through alkylene linkers of various length, and the resulting hybrids were evaluated for in vitro antileishmanial efficacy against Leishmania (L.) parasite of two strains. The hybrid 13, harboring a n-pentylene linker was uncovered as a leishmanicidal hit with micromolar activity against antimonial-resistant L. donovani, the causative of deadly visceral Leishmaniasis.