The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Mechanisms of action of isoniazid
Open accessAbstract
Summary: For decades after its introduction, the mechanisms of action of the front‐line antituberculosis therapeutic agent isoniazid (INH) remained unclear. Recent developments have shown that peroxidative activation of isoniazid by the mycobacterial enzyme KatG generates reactive species that form adducts with NAD+ and NADP+ that are potent inhibitors of lipid and nucleic acid biosynthetic enzymes. A direct role for some isoniazid‐derived reactive species, such as nitric oxide, in inhibiting mycobacterial metabolic enzymes has also been shown. The concerted effects of these activities – inhibition of cell wall lipid synthesis, depletion of nucleic acid pools and metabolic depression – drive the exquisite potency and selectivity of this agent. To understand INH action and resistance fully, a synthesis of knowledge is required from multiple separate lines of research – including molecular genetic approaches, in vitro biochemical studies and free radical chemistry – which is the intent of this review.
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Cited by
Virulence factors of the Mycobacterium tuberculosis complex
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A Survey of the Structures of US FDA Approved Combination Drugs
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“Among them, pemirolast is used to treat chronic asthma through inhibiting the antigen-induced release of inflammatory mediators [219]; isoniazid pyruvate is a metabolite of isoniazid [220]; nitrofurantoin is used to treat urinary tract infections via reduced bacterial flavoproteins to reactive intermediates, and eriod…”
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Metadata
- Authors
- Timmins, G. S., & Deretic, V.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2006-10-24
- Volume
- 62
- Issue
- 5
- Pages
- 1220-1227
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1987179105
- Cited by
- 421
- References
- 70
- FWCI
- 4.01
- Type
- journal article
- Language
- en
- Open access
- bronze
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