| Title |
Isosteres of hydroxypyridinethione as drug-like pharmacophores for metalloenzyme inhibition
|
|---|---|
| Published in |
JBIC Journal of Biological Inorganic Chemistry, July 2018
|
| DOI | 10.1007/s00775-018-1593-1 |
| Pubmed ID | |
| Authors |
Rebecca N. Adamek, Cy V. Credille, Benjamin L. Dick, Seth M. Cohen |
| Abstract |
Hydroxypyridinethiones (HOPTOs) are strong ligands for metal ions and potentially useful pharmacophores for inhibiting metalloenzymes relevant to human disease. However, HOPTOs have been sparingly used in drug discovery efforts due, in part, to concerns that this scaffold will act as a promiscuous, non-selective metalloenzyme inhibitor, as well as possess poor pharmacokinetics (PK), which may undermine drug candidates containing this functional group. To advance HOPTOs as a useful pharmacophore for metalloenzyme inhibitors, a library of 22 HOPTO isostere compounds has been synthesized and investigated. This library demonstrates that it is possible to maintain the core metal-binding pharmacophore (MBP) while generating diversity in structure, electronics, and PK properties. This HOPTO library has been screened against a set of four different metalloenzymes, demonstrating that while the same metal-binding donor atoms are maintained, there is a wide range of activity between metalloenzyme targets. Overall, this work shows that HOPTO isosteres are useful MBPs and valuable scaffolds for metalloenzyme inhibitors. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 28 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 25% |
| Student > Ph. D. Student | 5 | 18% |
| Student > Bachelor | 4 | 14% |
| Student > Master | 2 | 7% |
| Professor | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 8 | 29% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 12 | 43% |
| Biochemistry, Genetics and Molecular Biology | 4 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 7% |
| Agricultural and Biological Sciences | 1 | 4% |
| Chemical Engineering | 1 | 4% |
| Other | 0 | 0% |
| Unknown | 8 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 July 2018.
All research outputs
#21,180,380
of 23,842,189 outputs
Outputs from JBIC Journal of Biological Inorganic Chemistry
#590
of 664 outputs
Outputs of similar age
#288,392
of 328,556 outputs
Outputs of similar age from JBIC Journal of Biological Inorganic Chemistry
#15
of 17 outputs
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