ArticleScientific reports2016
Discovery of a Carbazole-Derived Lead Drug for Human African Trypanosomiasis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Identification of Substituted 4-Aminocinnolines as Broad-Spectrum Antiparasitic Agents.ACS infectious diseases · 2025Article
- Predicting anti-trypanosome effect of carbazole-derived compounds by powerful SVM with novel kernel function and comprehensive learning PSO.Antimicrobial agents and chemotherapy · 2024Article
- Multiparameter ranking of carbazoles for anti-trypanosome lead discovery.Frontiers in drug discovery · 2024Article
- Chemical Optimization of CBL0137 for Human African Trypanosomiasis Lead Drug Discovery.Journal of medicinal chemistry · 2023Article
- Structural diversity-guided optimization of carbazole derivatives as potential cytotoxic agents.Frontiers in chemistry · 2023Article
- Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.iScience · 2022Article
- Discovery of Novel Quinoline-Based Proteasome Inhibitors for Human African Trypanosomiasis (HAT).Journal of medicinal chemistry · 2022Article
- Cu(i)-catalyzed cross-coupling of primary amines with 2,2'-dibromo-1,1'-biphenyl for the synthesis of polysubstituted carbazole.RSC advances · 2022Article
- Synthesis of Carbazoles and Dihydrocarbazoles by a Divergent Cascade Reaction of Donor-Acceptor Cyclopropanes.Organic letters · 2021Article
- Synthesis of Carbazoles by a Diverted Bischler-Napieralski Cascade Reaction.Organic letters · 2021Article
- Apoferritin and Apoferritin-Capped Metal Nanoparticles Inhibit Arginine Kinase ofMolecules (Basel, Switzerland) · 2020Article
- A Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metabolite.Molecules (Basel, Switzerland) · 2020Article
- Improvement of Aqueous Solubility of Lapatinib-Derived Analogues: Identification of a Quinolinimine Lead for Human African Trypanosomiasis Drug Development.Journal of medicinal chemistry · 2019Article
- Anilinoquinoline based inhibitors of trypanosomatid proliferation.PLoS neglected tropical diseases · 2018Article
- Annulative π-extension of indoles and pyrroles with diiodobiaryls by Pd catalysis: rapid synthesis of nitrogen-containing polycyclic aromatic compounds.Chemical science · 2018Article
- Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors ofACS medicinal chemistry letters · 2018Article
- Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation.European journal of medicinal chemistry · 2017Article
- The Roles of Mast Cells in Parasitic Protozoan Infections.Frontiers in immunology · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The protozoan parasite Trypanosoma brucei causes the fatal illness human African trypanosomiasis (HAT). Standard of care medications currently used to treat HAT have severe limitations, and there is a need to find new chemical entities that are active against infections of T. brucei. Following a "drug repurposing" approach, we tested anti-trypanosomal effects of carbazole-derived compounds called "Curaxins". In vitro screening of 26 compounds revealed 22 with nanomolar potency against axenically cultured bloodstream trypanosomes. In a murine model of HAT, oral administration of compound 1 cured the disease. These studies established 1 as a lead for development of drugs against HAT. Pharmacological time-course studies revealed the primary effect of 1 to be concurrent inhibition of mitosis coupled with aberrant licensing of S-phase entry. Consequently, polyploid trypanosomes containing 8C equivalent of DNA per nucleus and three or four kinetoplasts were produced. These effects of 1 on the trypanosome are reminiscent of "mitotic slippage" or endoreplication observed in some other eukaryotes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.