ArticleJournal of medicinal chemistry2017
Rational Design of Selective Adenine-Based Scaffolds for Inactivation of Bacterial Histidine Kinases.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 19 citations in OpenAlex.
- Development of binding and activity inhibition assays for the antibiotic resistance-associated protein PhoQ.bioRxiv : the preprint server for biology · 2026Article
- Evaluation of expanded 2-aminobenzothiazole library as inhibitors of a model histidine kinase and virulence suppressors in Pseudomonas aeruginosa.Bioorganic chemistry · 2024Article
- Evaluation of Expanded 2-Aminobenzothiazole Library for Inhibition ofbioRxiv : the preprint server for biology · 2024Article
- Targeting multidrug resistantChemical science · 2023Article
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- Strategies to Attenuate the Competence Regulon inPeptide science (Hoboken, N.J.) · 2021Article
- Targeting a highly conserved domain in bacterial histidine kinases to generate inhibitors with broad spectrum activity.Current opinion in microbiology · 2021Review
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Synthesis of histidine kinase inhibitors and their biological properties.Medicinal research reviews · 2020Review
- Screening serine/threonine and tyrosine kinase inhibitors for histidine kinase inhibition.Bioorganic & medicinal chemistry · 2018Article
- Disarming the virulence arsenal ofChemical science · 2018Article
- Exploration of the Effects of γ-Phosphate-Modified ATP Analogues on Histidine Kinase Autophosphorylation.Biochemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Bacterial histidine kinases (HKs) are quintessential regulatory enzymes found ubiquitously in bacteria. Apart from their regulatory roles, they are also involved in the production of virulence factors and conferring resistance to various antibiotics in pathogenic microbes. We have previously reported compounds that inhibit multiple HKs by targeting the conserved catalytic and ATP-binding (CA) domain. Herein, we conduct a detailed structure-activity relationship assessment of adenine-based inhibitors using biochemical and docking methods. These studies have resulted in several observations. First, interaction of an inhibitor's amine group with the conserved active-site Asp is essential for activity and likely dictates its orientation in the binding pocket. Second, a N-NH-N triad in the inhibitor scaffold is highly preferred for binding to conserved Gly:Asp:Asn residues. Lastly, hydrophobic electron-withdrawing groups at several positions in the adenine core enhance potency. The selectivity of these inhibitors was tested against heat shock protein 90 (HSP90), which possesses a similar ATP-binding fold. We found that groups that target the ATP-lid portion of the catalytic domain, such as a six-membered ring, confer selectivity for HKs.
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.