ArticleJournal of medicinal chemistry2014
Structural basis for rational design of inhibitors targeting Trypanosoma cruzi sterol 14α-demethylase: two regions of the enzyme molecule potentiate its inhibition.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Enantioconvergent Chan-Evans-Lam C(spJournal of the American Chemical Society · 2026Article
- ExploringAntimicrobial agents and chemotherapy · 2026Article
- In vitro assays identified thiohydantoins with anti-trypanosomatid activity and molecular modelling studies indicated possible selective CYP51 inhibition.Scientific reports · 2025Article
- Updates on Mechanisms of Cytochrome P450 Catalysis of Complex Steroid Oxidations.International journal of molecular sciences · 2024Review
- Cytochrome P450 Enzymes as Drug Targets in Human Disease.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Identification of Potent and Selective Inhibitors ofJournal of medicinal chemistry · 2024Article
- Miconazole-like Scaffold is a Promising Lead forJournal of medicinal chemistry · 2023Article
- Drug Metabolism: A Half-Century Plus of Progress, Continued Needs, and New Opportunities.Drug metabolism and disposition: the biological fate of chemicals · 2023Article
- Inhibition of Cytochrome P450 Enzymes by Drugs-Molecular Basis and Practical Applications.Biomolecules & therapeutics · 2022Review
- Relaxed Substrate Requirements of Sterol 14α-Demethylase fromJournal of medicinal chemistry · 2021Article
- Planning new Trypanosoma cruzi CYP51 inhibitors using QSAR studies.Molecular diversity · 2021Article
- Synthesis, Absolute Configuration, Antibacterial, and Antifungal Activities of Novel BenzofurylMaterials (Basel, Switzerland) · 2020Article
- Validation of Human Sterol 14α-Demethylase (CYP51) Druggability: Structure-Guided Design, Synthesis, and Evaluation of Stoichiometric, Functionally Irreversible Inhibitors.Journal of medicinal chemistry · 2019Article
- Advances in preclinical approaches to Chagas disease drug discovery.Expert opinion on drug discovery · 2019Review
- In vitro evaluation of arylsubstituted imidazoles derivatives as antiprotozoal agents and docking studies on sterol 14α-demethylase (CYP51) from Trypanosoma cruzi, Leishmania infantum, and Trypanosoma brucei.Parasitology research · 2019Article
- CYP51 as drug targets for fungi and protozoan parasites: past, present and future.Parasitology · 2018Review
- Review
- Sterol 14α-Demethylase Structure-Based Design of VNI (( R)- N-(1-(2,4-Dichlorophenyl)-2-(1 H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)) Derivatives To Target Fungal Infections: Synthesis, Biological Evaluation, and Crystallographic Analysis.Journal of medicinal chemistry · 2018Article
- A convergent, scalable and stereoselective synthesis of azole CYP51 inhibitors.Tetrahedron letters · 2017Article
- Structural analyses ofThe Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Chagas disease, which was once thought to be confined to endemic regions of Latin America, has now gone global, becoming a new worldwide challenge with no cure available. The disease is caused by the protozoan parasite Trypanosoma cruzi, which depends on the production of endogenous sterols, and therefore can be blocked by sterol 14α-demethylase (CYP51) inhibitors. Here we explore the spectral binding parameters, inhibitory effects on T. cruzi CYP51 activity, and antiparasitic potencies of a new set of β-phenyl imidazoles. Comparative structural characterization of the T. cruzi CYP51 complexes with the three most potent inhibitors reveals two opposite binding modes of the compounds ((R)-6, EC50=1.2 nM, vs (S)-2/(S)-3, EC50=1.0/5.5 nM) and suggests the entrance into the CYP51 substrate access channel and the heme propionate-supporting ceiling of the binding cavity as two distinct areas of the protein that enhance molecular recognition and therefore could be used for the development of more effective antiparasitic drugs.
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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.