ArticleJournal of medicinal chemistry2015
Synthesis and Pharmacokinetic Evaluation of Siderophore Biosynthesis Inhibitors for Mycobacterium tuberculosis.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 31 citations in OpenAlex.
- Inhibition of Surfactin Biosynthesis in Bacillus Subtilis Using Cell-Permeable Adenylation Domain Inhibitors.Chembiochem : a European journal of chemical biology · 2025Article
- Targeting Siderophore Biosynthesis to Thwart Microbial Growth.International journal of molecular sciences · 2025Review
- Design and synthesis of a library of C2-substituted sulfamidoadenosines to probe bacterial permeability.Bioorganic & medicinal chemistry letters · 2024Article
- Rationally Designed Novel Phenyloxazoline Synthase Inhibitors: Chemical Synthesis and Biological Evaluation to Accelerate the Discovery of New Antimycobacterial Antibiotics.Molecules (Basel, Switzerland) · 2023Article
- Structural Study of a New MbtI-Inhibitor Complex: Towards an Optimized Model for Structure-Based Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2023Article
- TargetingRSC medicinal chemistry · 2023Review
- Iron Acquisition and Metabolism as a Promising Target for Antimicrobials (Bottlenecks and Opportunities): Where Do We Stand?International journal of molecular sciences · 2023Review
- Rational inhibitor design for Pseudomonas aeruginosa salicylate adenylation enzyme PchD.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Article
- Hit Compounds and Associated Targets in IntracellularMolecules (Basel, Switzerland) · 2022Article
- Signaling Natural Products from Human Pathogenic Bacteria.ACS infectious diseases · 2020Review
- Gram-scale preparation of the antibiotic lead compound salicyl-AMS, a potent inhibitor of bacterial salicylate adenylation enzymes.Methods in enzymology · 2020Article
- Article
- Clinical Pharmacokinetics and Pharmacodynamics of Eravacycline.Clinical pharmacokinetics · 2019Review
- Targeting adenylate-forming enzymes with designed sulfonyladenosine inhibitors.The Journal of antibiotics · 2019Review
- Kinetic Analyses of the Siderophore Biosynthesis Inhibitor Salicyl-AMS and Analogues as MbtA Inhibitors and Antimycobacterial Agents.Biochemistry · 2019Article
- Conformationally Constrained Cinnolinone Nucleoside Analogues as Siderophore Biosynthesis Inhibitors for Tuberculosis.ACS medicinal chemistry letters · 2018Article
- Post-translational Acetylation of MbtA Modulates Mycobacterial Siderophore Biosynthesis.The Journal of biological chemistry · 2016Article
- Synthesis and pharmacological evaluation of nucleoside prodrugs designed to target siderophore biosynthesis in Mycobacterium tuberculosis.Bioorganic & medicinal chemistry · 2016Article
- Investigation and conformational analysis of fluorinated nucleoside antibiotics targeting siderophore biosynthesis.The Journal of organic chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
MbtA catalyzes the first committed biosynthetic step of the mycobactins, which are important virulence factors associated with iron acquisition in Mycobacterium tuberculosis. MbtA is a validated therapeutic target for antitubercular drug development. 5'-O-[N-(Salicyl)sulfamoyl]adenosine (1) is a bisubstrate inhibitor of MbtA and exhibits exceptionally potent biochemical and antitubercular activity. However, 1 suffers from suboptimal drug disposition properties resulting in a short half-life (t(1/2)), low exposure (AUC), and low bioavailability (F). Four strategies were pursued to address these liabilities including the synthesis of prodrugs, increasing the pK(a) of the acyl-sulfonyl moiety, modulation of the lipophilicity, and strategic introduction of fluorine into 1. Complete pharmacokinetic (PK) analysis of all compounds was performed. The most successful modifications involved fluorination of the nucleoside that provided substantial improvements in t(1/2) and AUC. Increasing the pK(a) of the acyl-sulfonyl linker yielded incremental enhancements, while modulation of the lipophilicity and prodrug approaches led to substantially poorer PK parameters.
Indexed as
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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.