ArticleArchiv der Pharmazie2025
Unprecedented carbonic anhydrase inhibition mechanism: Targeting histidine 64 side chain through a halogen bond.
Article in Archiv der Pharmazie, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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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.
The trial behind it
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
6 citing papers in PubMed.
- Coumarin- and Dipicolylamine-Terpenoid Hybrids as Selective Carbonic Anhydrases IX and XII Inhibitors: Mechanistic Insights and Selective Anti-Cancer Potential.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Mechanisms of Carbonic Anhydrase Catalysis and Inhibition.Sub-cellular biochemistry · 2026Review
- Future Directions in Biotechnological and Pharmacological Applications of CAIs.Sub-cellular biochemistry · 2026Review
- Human Carbonic Anhydrase Inhibitors.ACS medicinal chemistry letters · 2025Review
- Computational insights into novel inhibitors: virtual screening of small molecules against human carbonic anhydrase II.Frontiers in chemistry · 2025Article
- Unprecedented carbonic anhydrase inhibition mechanism: Targeting histidine 64 side chain through a halogen bond.Archiv der Pharmazie · 2025Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
2,2'-Thio-bis(4,6-dichlorophenol), namely bithionol, is a small molecule endowed with a multifaceted bioactivity. Its peculiar polychlorinated phenolic structure makes it a suitable candidate to explore its potentialities in establishing interaction patterns with enzymes of MedChem interest, such as the human carbonic anhydrase (hCA) metalloenzymes. Herein, bithionol was tested on a panel of specific hCAs through the stopped-flow technique, showing a promising micromolar inhibitory activity for the hCA II isoform. X-ray crystallographic studies revealed an unprecedented halogen-bond interaction between one chlorine of bithionol and the N3(ε) atom of the hCA II catalytically active histidine residue, His64. Then, quantum mechanics calculations based on the fragment molecular orbital method allowed us to estimate the strength of this bond (~2.9 kcal/mol) and highlighted the contribution of a rich hydrophobic interaction network within the isoenzyme. Interestingly, the compound inactivity against the hCA III isoform, characterized by His64Lys and Leu198Phe mutations, supported the key role played by halogen bonding in the enzyme affinity. This finding might pave the way for the development of a new class of hCA inhibitors characterized by such chemical features, with the halogen bond being a key ligand-receptor interaction.
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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.