ArticlePloS one2018
Tetrahydrocarbazoles are a novel class of potent P-type ATPase inhibitors with antifungal activity.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Distinct Inhibitory Effects of Statin Lactones on CaMolecules (Basel, Switzerland) · 2026Article
- Tetrahydrocarbazole as a Versatile Scaffold in Drug Discovery: A Cross-Target SAR Analysis and Design Paradigms.Molecules (Basel, Switzerland) · 2026Review
- The Archetypal Gamma-Core Motif of Antimicrobial Cys-Rich Peptides Inhibits HInternational journal of molecular sciences · 2024Article
- The Antimicrobial Activity of Human Defensins at Physiological Non-Permeabilizing Concentrations Is Caused by the Inhibition of the Plasma Membrane HInternational journal of molecular sciences · 2024Article
- Fungal Plasma Membrane HJournal of fungi (Basel, Switzerland) · 2024Review
- THCz: Small molecules with antimicrobial activity that block cell wall lipid intermediates.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Structure of the hexameric fungal plasma membrane proton pump in its autoinhibited state.Science advances · 2021Article
- Structure and activation mechanism of the hexameric plasma membrane HNature communications · 2021Article
- A review of TNP-ATP in protein binding studies: benefits and pitfalls.Biophysical reports · 2021Review
- Cryo-Electron Tomography of Candida glabrata Plasma Membrane Proteins.Journal of fungi (Basel, Switzerland) · 2021Article
- Blockade of Oncogenic NOTCH1 with the SERCA Inhibitor CAD204520 in T Cell Acute Lymphoblastic Leukemia.Cell chemical biology · 2020Article
- Linking Biochemical and Structural States of SERCA: Achievements, Challenges, and New Opportunities.International journal of molecular sciences · 2020Review
- Endoplasmic Reticulum Calcium Pumps and Tumor Cell Differentiation.International journal of molecular sciences · 2020Review
- Molecular Characterization of Carbapenem Resistant Klebsiella pneumoniae and Klebsiella quasipneumoniae Isolated from Lebanon.Scientific reports · 2019Article
- Two inhibitors of yeast plasma membrane ATPase 1 (ScPma1p): toward the development of novel antifungal therapies.Journal of cheminformatics · 2018Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
We have identified a series of tetrahydrocarbazoles as novel P-type ATPase inhibitors. Using a set of rationally designed analogues, we have analyzed their structure-activity relationship using functional assays, crystallographic data and computational modeling. We found that tetrahydrocarbazoles inhibit adenosine triphosphate (ATP) hydrolysis of the fungal H+-ATPase, depolarize the fungal plasma membrane and exhibit broad-spectrum antifungal activity. Comparative inhibition studies indicate that many tetrahydrocarbazoles also inhibit the mammalian Ca2+-ATPase (SERCA) and Na+,K+-ATPase with an even higher potency than Pma1. We have located the binding site for this compound class by crystallographic structure determination of a SERCA-tetrahydrocarbazole complex to 3.0 Å resolution, finding that the compound binds to a region above the ion inlet channel of the ATPase. A homology model of the Candida albicans H+-ATPase based on this crystal structure, indicates that the compounds could bind to the same pocket and identifies pocket extensions that could be exploited for selectivity enhancement. The results of this study will aid further optimization towards selective H+-ATPase inhibitors as a new class of antifungal agents.
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