ArticleJournal of medicinal chemistry2016
The Rational Design, Synthesis, and Antimicrobial Properties of Thiophene Derivatives That Inhibit Bacterial Histidine Kinases.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 53 citations in OpenAlex.
- Two-component systems as potential therapeutic targets inAnnals of medicine · 2025Review
- IITR00803: a benzoxazole-nitrothiophene small molecule with broad-spectrum antibacterial potential.Microbiology spectrum · 2025Article
- Pd-, Cu-, and Ni-Catalyzed Reactions: A Comprehensive Review of the Efficient Approaches towards the Synthesis of Antibacterial Molecules.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Combatting Antibiotic-ResistantJournal of chemical information and modeling · 2024Article
- Bacterial Histidine Kinase and the Development of Its Inhibitors in the 21st Century.Antibiotics (Basel, Switzerland) · 2024Review
- Evaluation of Expanded 2-Aminobenzothiazole Library for Inhibition ofbioRxiv : the preprint server for biology · 2024Article
- Drug repositioning: doxazosin attenuates the virulence factors and biofilm formation in Gram-negative bacteria.Applied microbiology and biotechnology · 2023Article
- Antimicrobial Resistance: Two-Component Regulatory Systems and Multidrug Efflux Pumps.Antibiotics (Basel, Switzerland) · 2023Review
- Novel Thiazolylketenyl Quinazolinones as Potential Anti-MRSA Agents and Allosteric Modulator for PBP2a.Molecules (Basel, Switzerland) · 2023Article
- Microbial Genomics: Innovative Targets and Mechanisms.Antibiotics (Basel, Switzerland) · 2023Review
- Controlling of Bacterial Virulence: Evaluation of Anti-Virulence Activities of Prazosin againstAntibiotics (Basel, Switzerland) · 2022Article
- Polyphenols as Inhibitors of Antibiotic Resistant Bacteria-Mechanisms Underlying Rutin Interference with Bacterial Virulence.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Catalyst-Free Site Selective Hydroxyalkylation of 5-Phenylthiophen-2-amine with α-Trifluoromethyl Ketones through Electrophilic Aromatic Substitution.Molecules (Basel, Switzerland) · 2022Article
- Recent Advances in Histidine Kinase-Targeted Antimicrobial Agents.Frontiers in chemistry · 2022Review
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- Targeting a highly conserved domain in bacterial histidine kinases to generate inhibitors with broad spectrum activity.Current opinion in microbiology · 2021Review
- Synthesis, Structure Elucidation, Antibacterial Activities, and Synergistic Effects of Novel Juglone and Naphthazarin Derivatives Against Clinical Methicillin-ResistantFrontiers in chemistry · 2021Article
- Synthesis of histidine kinase inhibitors and their biological properties.Medicinal research reviews · 2020Review
- Quinazoline-Based Antivirulence Compounds Selectively TargetAntimicrobial agents and chemotherapy · 2019Article
- Novel narrow spectrum benzyl thiophene sulfonamide derivatives to control Campylobacter.The Journal of antibiotics · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The emergence of multidrug-resistant bacteria emphasizes the urgent need for novel antibacterial compounds targeting unique cellular processes. Two-component signal transduction systems (TCSs) are commonly used by bacteria to couple environmental stimuli to adaptive responses, are absent in mammals, and are embedded in various pathogenic pathways. To attenuate these signaling pathways, we aimed to target the TCS signal transducer histidine kinase (HK) by focusing on their highly conserved adenosine triphosphate-binding domain. We used a structure-based drug design strategy that begins from an inhibitor-bound crystal structure and includes a significant number of structurally simplifiying "intuitive" modifications to arrive at the simple achiral, biaryl target structures. Thus, ligands were designed, leading to a series of thiophene derivatives. These compounds were synthesized and evaluated in vitro against bacterial HKs. We identified eight compounds with significant inhibitory activities against these proteins, two of which exhibited broad-spectrum antimicrobial activity. The compounds were also evaluated as adjuvants for the treatment of resistant bacteria. One compound was found to restore the sensivity of these bacteria to the respective antibiotics.
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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.