ArticleJournal of medicinal chemistry2017
Structure-Based Optimization of Pyridoxal 5'-Phosphate-Dependent Transaminase Enzyme (BioA) Inhibitors that Target Biotin Biosynthesis in Mycobacterium tuberculosis.
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 21 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
21 citing papers in PubMed, 39 citations in OpenAlex.
- The Pyridoxal-5'-Phosphate-Dependent Enzymes ofACS infectious diseases · 2026Review
- Structure-Guided Development of a Potent BioA Inhibitor Validates Biotin Synthesis Inhibition as a Therapeutic Strategy for Tuberculosis.bioRxiv : the preprint server for biology · 2025Article
- Confronting the Antimicrobial Resistance Crisis in China: Emerging Superbugs, Genomic Surveillance, and Innovative Countermeasures.China CDC weekly · 2025Article
- Chemical language modeling with structured state space sequence models.Nature communications · 2024Article
- Pseudogenomic insights into the evolution of Mycobacterium ulcerans.BMC genomics · 2024Article
- Synthesis and Structure-Activity Relationships of a New Class of Oxadiazoles Targeting DprE1 as Antitubercular Agents.ACS medicinal chemistry letters · 2023Article
- Mycobacterial biotin biosynthesis counters airway alkalinity.Nature microbiology · 2023Article
- Biotin-dependent cell envelope remodelling is required for Mycobacterium abscessus survival in lung infection.Nature microbiology · 2023Article
- Three enigmatic BioH isoenzymes are programmed in the early stage of mycobacterial biotin synthesis, an attractive anti-TB drug target.PLoS pathogens · 2022Article
- Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.Antibiotics (Basel, Switzerland) · 2022Article
- Article
- Novel piperazine-chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Tuberculosis Drug Discovery: A Decade of Hit Assessment for Defined Targets.Frontiers in cellular and infection microbiology · 2021Review
- The primary step of biotin synthesis in mycobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Discovery of 2,6-Dimethylpiperazines as Allosteric Inhibitors of CPS1.ACS medicinal chemistry letters · 2020Article
- The Biotin Biosynthetic Pathway in Mycobacterium tuberculosis is a Validated Target for the Development of Antibacterial Agents.Current medicinal chemistry · 2020Review
- AFrontiers in microbiology · 2020Article
- Mimicking the human environment in mice reveals that inhibiting biotin biosynthesis is effective against antibiotic-resistant pathogens.Nature microbiology · 2020Article
- Cancer-targeted design of bioresponsive prodrug with enhanced cellular uptake to achieve precise cancer therapy.Drug delivery · 2018Article
- Hit Generation in TB Drug Discovery: From Genome to Granuloma.Chemical reviews · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The pyridoxal 5'-phosphate (PLP)-dependent transaminase BioA catalyzes the second step in the biosynthesis of biotin in Mycobacterium tuberculosis (Mtb) and is an essential enzyme for bacterial survival and persistence in vivo. A promising BioA inhibitor 6 containing an N-aryl, N'-benzoylpiperazine scaffold was previously identified by target-based whole-cell screening. Here, we explore the structure-activity relationships (SAR) through the design, synthesis, and biological evaluation of a systematic series of analogues of the original hit using a structure-based drug design strategy, which was enabled by cocrystallization of several analogues with BioA. To confirm target engagement and discern analogues with off-target activity, each compound was evaluated against wild-type (WT) Mtb in biotin-free and -containing medium as well as BioA under- and overexpressing Mtb strains. Conformationally constrained derivative 36 emerged as the most potent analogue with a K
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.