nalidixic acid

CHEBI:100147 ·resolve ·ANTIBACTERIAL ·EXACT SEEDED

A monocarboxylic acid comprising 1,8-naphthyridin-4-one substituted by carboxylic acid, ethyl and methyl groups at positions 3, 1, and 7, respectively. An orally administered antibacterial, it is used in the treatment of lower urinary-tract infections due to Gram-negative bacteria, including the majority of E. coli, Enterobacter, Klebsiella, and Proteus species. — ChEBI

Machine-generated and unreviewed. Identity, structure and cross-references come straight from ChEBI's and CARD's own data; no curator has signed off on this record yet.

Classification

fluoroquinolone antibioticARO:0000001

Strictly broader compounds or drug classes this molecule belongs to.

CHEBI:25384 CHEBI:25384
CHEBI:73537 CHEBI:73537
CHEBI:86324 CHEBI:86324
ARO:0000001 ARO:0000001

Chemical structure

Computed structure properties
Molecular formula	C12H12N2O3
Charge	0
Average mass	232.239 Da
Monoisotopic mass	232.08479 Da
Source	ChEBI
InChIKey	MHWLWQUZZRMNGJ-UHFFFAOYSA-N

SMILES

CCn1cc(C(=O)O)c(=O)c2ccc(C)nc21

InChI

InChI=1S/C12H12N2O3/c1-3-14-6-9(12(16)17)10(15)8-5-4-7(2)13-11(8)14/h4-6H,3H2,1-2H3,(H,16,17)

Also called

acide nalidixique (INN)— chebi
acido nalidixico (INN)— chebi
acidum nalidixicum (INN)— chebi
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid (EXACT_SYNONYM)— chebi
1,4-dihydro-1-ethyl-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (EXACT_SYNONYM)— chebi
1-Aethyl-7-methyl-1,8-naphthyridin-4-on-3-karbonsaeure (EXACT_SYNONYM)— chebi
1-Ethyl-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid (EXACT_SYNONYM)— chebi
1-ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (EXACT_SYNONYM)— chebi
1-ethyl-7-methyl-1,4-dihydro-1,8-naphthyridin-4-one-3-carboxylic acid (EXACT_SYNONYM)— chebi
3-carboxy-1-ethyl-7-methyl-1,8-naphthyridin-4-one (EXACT_SYNONYM)— chebi
NALIDIXIC ACID (EXACT_SYNONYM)— chebi
Nalidixic acid (EXACT_SYNONYM)— chebi
nalidixin (EXACT_SYNONYM)— aro

Cross-references

Equivalent identifiers for this same structure in other resources.

ARO:3000661
cas:389-08-2
drugbank:DB00779
drugcentral:1875
kegg.compound:C05079
kegg.drug:D00183
lincs.smallmolecule:LSM-5590
patent:BE612258
patent:US3590036
pdb-ccd:NIX
reaxys:750515
vsdb:1880
wikipedia.en:Nalidixic_Acid
chembl:CHEMBL5
pubchem.compound:4421

Activity roles

Every antimicrobial role a source asserts for this compound — the unreduced evidence behind its antimicrobial_class.

CHEBI:33281 CHEBI:33281
CHEBI:36047 CHEBI:36047

Source concepts

Every upstream concept that resolved to this record. The merge is the product: this is what shows ChEBI and CARD are describing the same structure.

Upstream concepts merged into this record
Source	Native ID	Label	Minted CURIE	Version
ARO	`ARO:3000661`	nalidixic acid	`antibioticmech:aro-4cf71250ed`	2026-08-30
CHEBI	`CHEBI:100147`	nalidixic acid	`antibioticmech:chebi-561a3b207f`	2026-08-30

Molecular targets

The molecular entity or process this compound acts on. Each target carries evidence — this is a mechanistic claim, not a classification.

fluoroquinolone sensitive gyrA PROTEIN DIRECT_BINDING_TARGET

ARO:3000733

CARD/ARO database assertion; target organism, strain, and assay are not specified. ARO explicitly describes ligand binding to gyrase subunit A. Evidence status: PRIMARY_EVIDENCE_NEEDED. Source: CARD_ARO 2026-08-30 (retrieved 2026-08-30).

ARO:3000733 (CARD/ARO asserts targeted_by_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)

DNA topoisomerase 4 subunit A [V210L]/B PROTEIN_COMPLEX MEASURED_TARGET_ASSOCIATION

BindingDB quantitative measurement in the named target organism; source assay descriptions and identifiers are retained per measurement. Evidence status: PRIMARY_EVIDENCE. Source: BINDINGDB 2026-09 (retrieved 2026-08-31).

Bacillus subtilis NCBITaxon:1423

Quantitative measurements
Type	Reported value	Assay	BindingDB IDs	Reference
IC50	1090000 nM	DNA Topoisomerase IV Assay The 50% inhibitory concentration (IC50) is defined as the concentration of compound that inhibits the decatenation of kinetoplast DNA by 50%.	`RSID 39230` `assay 2532_2` `monomer 21691`	`PMID:17074800`

Organism-specific examples
Protein	Gene	Organism	Entry
DNA topoisomerase 4 subunit A `UniProtKB:Q45066`	—	Bacillus subtilis	REVIEWED
DNA topoisomerase 4 subunit B `UniProtKB:Q59192`	—	Bacillus subtilis	REVIEWED

PMID:17074800 (BindingDB literature-curated quantitative target measurement; source value, assay text, reaction-set ID, and target organism retained.)

Mechanism summary

Mode of action: NUCLEIC_ACID_SYNTHESIS_INHIBITION microbial target — CURATOR: Confirmed as bacterial DNA gyrase poisoning after primary nalidixic acid mechanism review. PMID:200930.
Clinical status: APPROVED

Resistance mechanisms

35 known routes by which microbes resist this compound, grounded in ARO where CARD models them. Grouped by mechanism type — expand a group to see its determinants.

ANTIBIOTIC_TARGET_ALTERATION 27

ANTIBIOTIC_TARGET_ALTERATION
Determinant	ARO ID	Organism	Gene families	Evidence
Acinetobacter baumannii gyrA conferring resistance to fluoroquinolones	ARO:3003817	not organism-specific	—	ARO:3003817 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Acinetobacter baumannii parC conferring resistance to fluoroquinolones	ARO:3003818	not organism-specific	—	ARO:3003818 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Bartonella bacilliformis gyrA conferring resistance to fluoroquinolones	ARO:3003297	not organism-specific	—	ARO:3003297 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Escherichia coli gyrA conferring resistance to fluoroquinolones	ARO:3003294	not organism-specific	—	ARO:3003294 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Escherichia coli parC conferring resistance to fluoroquinolones	ARO:3003308	not organism-specific	—	ARO:3003308 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Escherichia coli parE conferring resistance to fluoroquinolones	ARO:3003316	not organism-specific	—	ARO:3003316 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Escherichia coli soxR with mutation conferring antibiotic resistance	ARO:3003381	not organism-specific	—	ARO:3003381 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Morganella morganii gyrB conferring resistance to fluoroquinolones	ARO:3003306	not organism-specific	—	ARO:3003306 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Mycobacterium leprae gyrA conferring resistance to fluoroquinolones	ARO:3003298	not organism-specific	—	ARO:3003298 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Mycobacterium leprae gyrB conferring resistance to fluoroquinolones	ARO:3003304	not organism-specific	—	ARO:3003304 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Mycobacterium tuberculosis gyrA conferring resistance to fluoroquinolones	ARO:3003295	not organism-specific	—	ARO:3003295 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Mycobacterium tuberculosis gyrB with mutation conferring resistance to fluoroquinolones	ARO:3003459	not organism-specific	—	ARO:3003459 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Mycoplasma hominis parC conferring resistance to fluoroquinolones	ARO:3003310	not organism-specific	—	ARO:3003310 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Salmonella enterica gyrA conferring resistance to fluoroquinolones	ARO:3003926	not organism-specific	—	ARO:3003926 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Salmonella enterica parC conferring resistance to fluoroquinolones	ARO:3003939	not organism-specific	—	ARO:3003939 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Salmonella isangi gyrA conferring resistance to fluoroquinolones	ARO:3007751	not organism-specific	—	ARO:3007751 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Salmonella isangi gyrB conferring resistance to fluoroquinolones	ARO:3007752	not organism-specific	—	ARO:3007752 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Salmonella serovars gyrB conferring resistance to fluoroquinolones	ARO:3003307	not organism-specific	—	ARO:3003307 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Salmonella serovars parE conferring resistance to fluoroquinolones	ARO:3003317	not organism-specific	—	ARO:3003317 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Shigella flexneri gyrA conferring resistance to fluoroquinolones	ARO:3003940	not organism-specific	—	ARO:3003940 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Shigella flexneri parC conferring resistance to fluoroquinolones	ARO:3003941	not organism-specific	—	ARO:3003941 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Staphylococcus aureus gyrA conferring resistance to fluoroquinolones	ARO:3003296	not organism-specific	—	ARO:3003296 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Staphylococcus aureus parC conferring resistance to fluoroquinolones	ARO:3003312	not organism-specific	—	ARO:3003312 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Staphylococcus aureus parE conferring resistance to fluoroquinolones	ARO:3003315	not organism-specific	—	ARO:3003315 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Streptococcus pneumoniae parC conferring resistance to fluoroquinolones	ARO:3003311	not organism-specific	—	ARO:3003311 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Ureaplasma urealyticum gyrB conferring resistance to fluoroquinolones	ARO:3003305	not organism-specific	—	ARO:3003305 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Ureaplasma urealyticum parC conferring resistance to fluoroquinolones	ARO:3003309	not organism-specific	—	ARO:3003309 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)

ANTIBIOTIC_EFFLUX 5

ANTIBIOTIC_EFFLUX
Determinant	ARO ID	Organism	Gene families	Evidence
Acinetobacter baumannii AbaQ	ARO:3004574	not organism-specific	—	ARO:3004574 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
EmrAB-TolC	ARO:3000344	not organism-specific	—	ARO:3000344 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
QepA4	ARO:3004379	not organism-specific	—	ARO:3004379 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
mdeA	ARO:3007011	not organism-specific	—	ARO:3007011 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
putative nickel/cobalt transporter	ARO:3007659	not organism-specific	—	ARO:3007659 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)

REDUCED_PERMEABILITY 2

REDUCED_PERMEABILITY
Determinant	ARO ID	Organism	Gene families	Evidence
Escherichia coli LamB	ARO:3004126	not organism-specific	—	ARO:3004126 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)
Escherichia coli mipA	ARO:3004127	not organism-specific	—	ARO:3004127 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)

ANTIBIOTIC_TARGET_PROTECTION 1

ANTIBIOTIC_TARGET_PROTECTION
Determinant	ARO ID	Organism	Gene families	Evidence
quinolone resistance protein (qnr)	ARO:3000419	not organism-specific	—	ARO:3000419 (CARD/ARO asserts confers_resistance_to_antibiotic ARO:3000661 (nalidixic acid); database assertion, not a primary citation.)

Causal graphs

Evidence-backed mechanism graphs: how the compound reaches its target, what the target does, and how the effect propagates to growth inhibition or death.

Nalidixic acid poisons bacterial DNA gyrase MECHANISTIC

Nalidixic acid acts on the GyrA-containing bacterial DNA gyrase complex, trapping a protein-linked DNA cleavage state that blocks completion of DNA topology-changing reactions.

Nodes — nalidixic_acid_gyrase_cleavage_complex
Node	Label	Type	Grounding
`nalidixic_acid`	nalidixic acid	COMPOUND	`CHEBI:100147`
`dna_gyrase`	bacterial DNA gyrase	GENE_OR_PROTEIN	`ARO:3000733`
`gyrase_dna_cleavage_complex`	DNA gyrase covalent DNA cleavage complex	STATE	REVIEWED_LABEL_ONLY
`dna_religation`	DNA gyrase DNA religation	MOLECULAR_FUNCTION	REVIEWED_LABEL_ONLY
`dna_topology_control`	bacterial DNA topology control	BIOLOGICAL_PROCESS	REVIEWED_LABEL_ONLY

Edges — nalidixic_acid_gyrase_cleavage_complex
Subject	Predicate	Object	Evidence
`nalidixic_acid`	stabilizes	`gyrase_dna_cleavage_complex`	PMID:200930 (Sugino and colleagues showed nalidixic and oxolinic acids inhibit E. coli DNA gyrase and induce a relaxation-complex analogue.)
`dna_gyrase`	participates in	`gyrase_dna_cleavage_complex`	PMID:200930 (Purified NalA/GyrA restored nalidixic acid sensitivity to DNA gyrase activity in biochemical assays.)
`gyrase_dna_cleavage_complex`	inhibits	`dna_religation`	PMID:200930 (Nalidixic acid-induced gyrase complexes generated covalently protein-linked linear DNA after detergent treatment.)
`dna_religation`	supports	`dna_topology_control`	PMID:200930 (The nalidixic acid-sensitive NalA/GyrA protein participated in DNA gyrase supertwisting and ATP-independent DNA relaxation.)

Curation history

SEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources
Seeded from data/raw/ inventories (ARO, CHEBI)
RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources
Re-seeded from updated data/raw/ inventories
RESEEDED_FROM_SOURCES 2026-08-30 · seed_from_sources
Re-seeded from updated data/raw/ inventories
RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources
Re-seeded from updated data/raw/ inventories
RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources
Re-seeded from updated data/raw/ inventories
RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources
Re-seeded from updated data/raw/ inventories
RESEEDED_FROM_SOURCES 2026-08-31 · seed_from_sources
Re-seeded from updated data/raw/ inventories
CURATED_CAUSAL_GRAPH 2026-09-04 · codex · LLM-assisted
Added a PMID-supported causal graph for nalidixic acid poisoning of bacterial DNA gyrase and marked the coarse target scope as curator-reviewed.

Provenance

Seeded by scripts/seed_from_sources.py from the committed inventories in data/raw/. View the record.