ArticleScientific reports2018
A multitarget approach to drug discovery inhibiting Mycobacterium tuberculosis PyrG and PanK.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
- Reference-based chemical-genetic interaction profiling to elucidate small molecule mechanism of action in Mycobacterium tuberculosis.Nature communications · 2025Article
- Identifying Opportunity Targets in Gram-Negative Pathogens for Infectious Disease Mitigation.ACS central science · 2025Review
- Structural Basis of Bifunctional CTP/dCTP Synthase.Journal of molecular biology · 2024Article
- Architecture of CTPS filament networks revealed by cryo-electron tomography.Experimental cell research · 2024Article
- The Impact of Developmental and Metabolic Cues on Cytoophidium Formation.International journal of molecular sciences · 2024Review
- Article
- In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain.Current issues in molecular biology · 2024Article
- Polypharmacology-Driven Discovery and Design of Highly Selective, Dual and Multitargeting Inhibitors ofCurrent drug targets · 2024Review
- In silico study of bioactive compounds derived from Indonesian marine invertebrates as a novel antituberculosis agent.Turkish journal of medical sciences · 2024Article
- Unrealized targets in the discovery of antibiotics for Gram-negative bacterial infections.Nature reviews. Drug discovery · 2023Review
- In-silico and in-vitro assessments of some fabaceae, rhamnaceae, apocynaceae, and anacardiaceae species against Mycobacterium tuberculosis H37Rv and triple-negative breast cancer cells.BMC complementary medicine and therapies · 2023Article
- Expanding the knowledge around antitubercular 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides: Hit-to-lead optimization and release of a novel antitubercular chemotype via scaffold derivatization.European journal of medicinal chemistry · 2023Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
- Article
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
- Antitubercular, Cytotoxicity, and Computational Target Validation of Dihydroquinazolinone Derivatives.Antibiotics (Basel, Switzerland) · 2022Article
- GTP-Dependent Regulation of CTP Synthase: Evolving Insights into Allosteric Activation and NHBiomolecules · 2022Review
- A d-Phenylalanine-Benzoxazole Derivative Reveals the Role of the Essential Enzyme Rv3603c in the Pantothenate Biosynthetic Pathway ofACS infectious diseases · 2022Article
- Machine Learning Models forMolecular pharmaceutics · 2022Article
- Article
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacterium tuberculosis, the etiological agent of the infectious disease tuberculosis, kills approximately 1.5 million people annually, while the spread of multidrug-resistant strains is of great global concern. Thus, continuous efforts to identify new antitubercular drugs as well as novel targets are crucial. Recently, two prodrugs activated by the monooxygenase EthA, 7947882 and 7904688, which target the CTP synthetase PyrG, were identified and characterized. In this work, microbiological, biochemical, and in silico methodologies were used to demonstrate that both prodrugs possess a second target, the pantothenate kinase PanK. This enzyme is involved in coenzyme A biosynthesis, an essential pathway for M. tuberculosis growth. Moreover, compound 11426026, the active metabolite of 7947882, was demonstrated to directly inhibit PanK, as well. In an independent screen of a compound library against PyrG, two additional inhibitors were also found to be active against PanK. In conclusion, these direct PyrG and PanK inhibitors can be considered as leads for multitarget antitubercular drugs and these two enzymes could be employed as a "double-tool" in order to find additional hit compounds.
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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.