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nargenicin A1   Click here for help

GtoPdb Ligand ID: 14528

Synonyms: CP 47,444
PDB Ligand
Compound class: Natural product
Comment: Nargenicin A1 is a macrolide antibacterial, first isolated from the soil-dwelling actinomycete Nocardia argentinensis [1]. It has narrow-spectrum Gram-positive antibacterial activity (principally anti-Staphylococcus activity), inhibiting bacterial DNA replication by targeting DNA polymerase III subunit alpha (DnaE) [3]. A more recent study has found that Nargenicin A1 has antimycobacterial activity and is an inhibitor of Mycobacterium tuberculosis DnaE1 [2].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 5
Topological polar surface area 123.55
Molecular weight 515.6
XLogP 1.14
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES C[C@@H]1/C=C(\C)/[C@@]23[C@]([H])(C=C[C@]4([H])[C@@]3([H])[C@@H]([C@@H](C)[C@H]([C@@H]4O2)OC(=O)C5=CC=CN5)O)C[C@@H](C(=O)O[C@]1([H])[C@@H](C)O)OC
Isomeric SMILES C/C=1/[C@@]23O[C@H]4[C@@H]([C@@H]([C@H]([C@]2([H])[C@@]4([H])C=C[C@]3([H])C[C@H](OC)C(O[C@]([C@@H](/C1)C)([H])[C@H](O)C)=O)O)C)OC(C5=CC=CN5)=O
InChI InChI=1S/C28H37NO8/c1-13-11-14(2)28-17(12-20(34-5)27(33)35-23(13)16(4)30)8-9-18-21(28)22(31)15(3)24(25(18)37-28)36-26(32)19-7-6-10-29-19/h6-11,13,15-18,20-25,29-31H,12H2,1-5H3/b14-11+/t13-,15-,16-,17-,18-,20+,21+,22-,23+,24-,25-,28+/m1/s1
InChI Key YEUSSARNQQYBKH-SIMZXIQRSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Celmer WD, Chmurny GN, Moppett CE, Ware Rs, Watts PC, Whipple EB. (1980)
Structure of natural antibiotic CP-47,444.
J. Am. Chem. Soc., 102 (12): 4203-4209. DOI: 10.1021/ja00532a036
2. Chengalroyen MD, Mason MK, Borsellini A, Tassoni R, Abrahams GL, Lynch S, Ahn YM, Ambler J, Young K, Crowley BM et al.. (2022)
DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in Mycobacterium tuberculosis.
ACS Infect Dis, 8 (3): 612-625. [PMID:35143160]
3. Painter RE, Adam GC, Arocho M, DiNunzio E, Donald RG, Dorso K, Genilloud O, Gill C, Goetz M, Hairston NN et al.. (2015)
Elucidation of DnaE as the Antibacterial Target of the Natural Product, Nargenicin.
Chem Biol, 22 (10): 1362-73. [PMID:26456734]