ArticlePloS one2020
Mycobacterium tuberculosis thymidylate synthase (ThyX) is a target for plumbagin, a natural product with antimycobacterial activity.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- The Oxidase Reaction of Flavin-Dependent Thymidylate Synthase Reveals the Nature of Inhibitor Binding.Biochemistry · 2025Article
- Carglumic acid and mesalazine as potential anti-mycobacterial agents: a spectroscopic study for repurposing drugs againstMicrobiology spectrum · 2025Article
- Natural Products with Potent Antimycobacterial Activity (2000-2024): A Review.Molecules (Basel, Switzerland) · 2025Review
- Selected Medicinal Plants Used in the Treatment and Management of Tuberculosis and Related Symptoms in South Africa.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Pharmacological Features and Therapeutic Implications of Plumbagin in Cancer and Metabolic Disorders: A Narrative Review.Nutrients · 2024Review
- Article
- Plant antibacterials: The challenges and opportunities.Heliyon · 2024Review
- Tackling Nontuberculous Mycobacteria by Repurposable Drugs and Potential Leads from Natural Products.Current topics in medicinal chemistry · 2024Review
- Plumbagin: A Promising In Vivo Antiparasitic Candidate againstBiomedicines · 2023Article
- Biosynthesis of ansamitocin P-3 incurs stress on the producing strain Actinosynnema pretiosum at multiple targets.Communications biology · 2023Article
- Plumbagin, a Natural Compound with Several Biological Effects and Anti-Inflammatory Properties.Life (Basel, Switzerland) · 2023Review
- Medicinal Plants as Therapeutic Alternatives to CombatAntibiotics (Basel, Switzerland) · 2023Review
- Natural-Product-Based Solutions for Tropical Infectious Diseases.Clinical microbiology reviews · 2021Review
- Plumbagin can potently enhance the activity of xanthine oxidase: in vitro, in vivo and in silico studies.BMC pharmacology & toxicology · 2021Article
- Screening and Identification of a Novel Anti-tuberculosis Compound That Targets Deoxyuridine 5'-Triphosphate Nucleotidohydrolase.Frontiers in microbiology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plumbagin derived from the plant Plumbago indica, known as Chitrak in India, is an example of a medicinal compound used traditionally to cure a variety of ailments. Previous reports have indicated that it can inhibit the growth of Mycobacterium tuberculosis (Mtb), the causative agent of the deadly disease TB. In this investigation, we provide an insight into its mode of action. We show here that a significant mycobacterial target that is inhibited by plumbagin is the enzyme ThyX, a form of thymidylate synthase, that is responsible for the synthesis of dTMP from dUMP in various bacterial pathogens, including Mtb. Using a purified preparation of the recombinant version of Mtb ThyX, we demonstrate that plumbagin, a 2,4 napthoquinone, but not lawsone, a structurally related medicinal compound, inhibits its activity in vitro. We also show that the intracellular [dTTP]/[dATP] ratio in Mycobacterium smegmatis (Msm) cells decrease upon treatment with plumbagin, and this, in turn, leads to cell death. Such a conclusion is supported by the observation that over-expression of thyx in the plumbagin treated Msm cells leads to the restoration of viability. The results of our investigation indicate that plumbagin kills mycobacterial cells primarily by targeting ThyX, a vital enzyme required for their survival.
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