ArticleJournal of medicinal chemistry2014
Exploring the influence of the protein environment on metal-binding pharmacophores.
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 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 31 citations in OpenAlex.
- Design and synthesis of non-hydroxamate lipophilic inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR):RSC advances · 2024Article
- Control of metalloenzyme activity using photopharmacophores.Coordination chemistry reviews · 2024Article
- Development of LpxH Inhibitors Chelating the Active Site Dimanganese Metal Cluster of LpxH.ChemMedChem · 2023Article
- Hydroxypyrone derivatives in drug discovery: from chelation therapy to rational design of metalloenzyme inhibitors.RSC medicinal chemistry · 2022Review
- A multiscale approach to predict the binding mode of metallo beta-lactamase inhibitors.Proteins · 2022Article
- Organoruthenium Complexes with Benzo-Fused Pyrithiones Overcome Platinum Resistance in Ovarian Cancer Cells.Cancers · 2021Article
- Structural Isomerism and Enhanced Lipophilicity of Pyrithione Ligands of Organoruthenium(II) Complexes Increase Inhibition on AChE and BuChE.International journal of molecular sciences · 2020Article
- Structure-Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease.Journal of medicinal chemistry · 2018Article
- Isosteres of hydroxypyridinethione as drug-like pharmacophores for metalloenzyme inhibition.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
- A Bioinorganic Approach to Fragment-Based Drug Discovery Targeting Metalloenzymes.Accounts of chemical research · 2017Article
- Effect of donor atom identity on metal-binding pharmacophore coordination.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2017Article
- Fragment-Based Approaches to the Development of Mycobacterium tuberculosis CYP121 Inhibitors.Journal of medicinal chemistry · 2016Article
- Investigation of the salicylaldehyde thiosemicarbazone scaffold for inhibition of influenza virus PA endonuclease.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The binding of a series of metal-binding pharmacophores (MBPs) related to the ligand 1-hydroxypyridine-2-(1H)-thione (1,2-HOPTO) in the active site of human carbonic anhydrase II (hCAII) has been investigated. The presence and/or position of a single methyl substituent drastically alters inhibitor potency and can result in coordination modes not observed in small-molecule model complexes. It is shown that this unexpected binding mode is the result of a steric clash between the methyl group and a highly ordered water network in the active site that is further stabilized by the formation of a hydrogen bond and favorable hydrophobic contacts. The affinity of MBPs is dependent on a large number of factors including donor atom identity, orientation, electrostatics, and van der Waals interactions. These results suggest that metal coordination by metalloenzyme inhibitors is a malleable interaction and that it is thus more appropriate to consider the metal-binding motif of these inhibitors as a pharmacophore rather than a "chelator". The rational design of inhibitors targeting metalloenzymes will benefit greatly from a deeper understanding of the interplay between the variety of forces governing the binding of MBPs to active site metal ions.
Indexed as
Identifiers
What OpenQuestion holds
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.