ArticleJournal of medicinal chemistry2013
Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma cruzi CYP51 as anti-chagas agents.
Article in Journal of medicinal chemistry, 2013. 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
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- N-substituted-4-(pyridin-4-ylalkyl)piperazine-1-carboxamides and related compounds as Leishmania CYP51 and CYP5122A1 inhibitors.Bioorganic & medicinal chemistry · 2024Article
- Aminopyridines in the development of drug candidates against protozoan neglected tropical diseases.Future medicinal chemistry · 2024Review
- 1,3-Diphenylureido hydroxamate as a promising scaffold for generation of potent antimalarial histone deacetylase inhibitors.Scientific reports · 2023Article
- The Evaluation of l-Tryptophan Derivatives as Inhibitors of the l-Type Amino Acid Transporter LAT1 (SLC7A5).ChemMedChem · 2022Article
- Recent Progress in the Development of Indole-Based Compounds Active against Malaria, Trypanosomiasis and Leishmaniasis.Molecules (Basel, Switzerland) · 2022Review
- Planning new Trypanosoma cruzi CYP51 inhibitors using QSAR studies.Molecular diversity · 2021Article
- Domain-Swap Dimerization ofMolecular pharmacology · 2020Article
- Computational approaches for drug discovery against trypanosomatid-caused diseases.Parasitology · 2020Review
- Donepezil + chromone + melatonin hybrids as promising agents for Alzheimer's disease therapy.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- 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
- Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias.Journal of medicinal chemistry · 2018Article
- Development of Mithramycin Analogues with Increased Selectivity toward ETS Transcription Factor Expressing Cancers.Journal of medicinal chemistry · 2018Article
- 3-pyridyl inhibitors with novel activity against Trypanosoma cruzi reveal in vitro profiles can aid prediction of putative cytochrome P450 inhibition.Scientific reports · 2018Article
- 4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection.PLoS neglected tropical diseases · 2017Article
- Interactions between 4-aminoquinoline and heme: Promising mechanism against Trypanosoma cruzi.International journal for parasitology. Drugs and drug resistance · 2016Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors.Journal of medicinal chemistry · 2016Article
- Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.Antimicrobial agents and chemotherapy · 2015Article
- Utilizing Chemical Genomics to Identify Cytochrome b as a Novel Drug Target for Chagas Disease.PLoS pathogens · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
A new series of 4-aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) has been developed using structure-based drug design as well as structure-property relationship (SPR) analyses. The screening hit starting point, LP10 (KD ≤ 42 nM; EC50 = 0.65 μM), has been optimized to give the potential leads 14t, 27i, 27q, 27r, and 27t, which have low-nanomolar binding affinity to TcCYP51 and significant activity against T. cruzi amastigotes cultured in human myoblasts (EC50 = 14-18 nM for 27i and 27r). Many of the optimized compounds have improved microsome stability, and most are selective against human CYPs 1A2, 2D6, and 3A4 (<50% inhibition at 1 μM). A rationale for the improvement in microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of 14t with the Trypanosoma brucei CYP51 (TbCYP51) orthologue has been characterized by X-ray structure analysis.
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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.