A series of novel 3-nitro-1H-1,2,4-triazole-based (and in some cases 2-nitro-1H-imidazole-based) amides and sulfonamides were characterized for their in vitro antitrypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1H-1,2,4-triazoles) displayed significant activity against Trypanosoma cruzi intracellular amastigotes (IC(50) ranging from 28 nM to 3.72 μM) without concomitant toxicity to L6 host cells (selectivity 66-2782). Twenty-three of these active compounds were more potent (up to 58-fold) than the reference drug benznidazole, tested in parallel. In addition, nine nitrotriazoles which were moderately active (0.5 μM ≤ IC(50) < 6.0 μM) against Trypanosoma brucei rhodesiense trypomastigotes were 5-31-fold more active against bloodstream-form Trypanosoma brucei brucei trypomastigotes engineered to overexpress reduced nicotinamide adenine dinucleotide dependent nitroreductase. Finally, three nitrotriazoles displayed a moderate activity against the axenic form of Leishmania donovani . Therefore, 3-nitro-1H-1,2,4-triazole-based amides and sulfonamides are potent antitrypanosomal agents.
Molecular characterization of susceptible and naturally resistant strains of Trypanosoma cruzi to benznidazole and nifurtimox
Nitrofuran drugs as common subversive substrates of Trypanosoma cruzi lipoamide dehydrogenase and trypanothione reductase
Inhibition of Trypanosoma cruzi trypanothione reductase by acridines: kinetic studies and structure-activity relationships
Design, synthesis, and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors
Oxidative stress and antioxidant defenses: a target for the treatment of diseases caused by parasitic protozoa
Synthesis and in vitro trichomonicidal, giardicidal and amebicidal activity of N-acetamide(sulfonamide)-2-methyl-4-nitro-1H-imidazoles
Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy
Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies
New potent 5-nitroindazole derivatives as inhibitors of Trypanosoma cruzi growth: synthesis, biological evaluation, and mechanism of action studies
The Atlas of human African trypanosomiasis: a contribution to global mapping of neglected tropical diseases
Genome-wide RNAi screens in African trypanosomes identify the nifurtimox activator NTR and the eflornithine transporter AAT6
Nifurtimox activation by trypanosomal type I nitroreductases generates cytotoxic nitrile metabolites.
Synthesis and structure-activity relationships of nitrobenzyl phosphoramide mustards as nitroreductase-activated prodrugs
Novel 3-nitro-1H-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles as antichagasic agents
Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Potential Anticonvulsant Agents
Novel nitro(triazole/imidazole)-based heteroarylamides/sulfonamides as potential antitrypanosomal agents
Synthesis, characterization and in vitro antitrypanosomal activities of new carboxamides bearing quinoline moiety
Carbonic Anhydrase Inhibitory Potential of 1,2,4-triazole-3-thione Derivatives of Flurbiprofen, Ibuprofen and 4-tert-butylbenzoic Hydrazide: Design, Synthesis, Characterization, Biochemical Evaluation, Molecular Docking and Dynamic Simulation Studies
Synthesis, characterization and anti-inflammatory activity evaluation of 1,2,4-triazole and its derivatives as a potential scaffold for the synthesis of drugs against prostaglandin-endoperoxide synthase.
A novel C2 symmetric chiral stationary phase with N-[(4-Methylphenyl)sulfonyl]-l-leucine as chiral side chains.
Straightforward Access to Anthrone Functionalized Benzylic Amines via Organocatalytic 1,2-Addition of Anthrones to Imines at Ambient Temperature.
1,2,4-Triazole-based benzothiazole/benzoxazole derivatives: Design, synthesis, p38α MAP kinase inhibition, anti-inflammatory activity and molecular docking studies
African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.