chlorotonil A   Click here for help

GtoPdb Ligand ID: 13589

Antimalarial Ligand
Compound class: Natural product
Comment: Chlorotonil A is a macrolide produced by the myxobacterium Sorangium cellulosum [2]. It has antibacterial activity against Gram-positive bacteria, antifungal activity and antimalarial activity.

The Malaria tab on this ligand page provides additional curator comments of relevance to the Guide to MALARIA PHARMACOLOGY.
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 4
Hydrogen bond donors 0
Rotatable bonds 0
Topological polar surface area 60.44
Molecular weight 479.44
XLogP 6.03
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 CC1=C[C@@H](C)[C@@H]2[C@H](C=C[C@H]3[C@H](C)/C=C\C=C\[C@H](C)OC(=O)[C@@H](C)C(=O)C(C(=O)[C@H]32)(Cl)Cl)C1
Isomeric SMILES C[C@@H]1/C=C\C=C\[C@@H](OC(=O)[C@H](C(=O)C(C(=O)[C@@H]2[C@H]1C=C[C@H]3[C@H]2[C@@H](C=C(C3)C)C)(Cl)Cl)C)C
InChI InChI=1S/C26H32Cl2O4/c1-14-12-16(3)21-19(13-14)10-11-20-15(2)8-6-7-9-17(4)32-25(31)18(5)23(29)26(27,28)24(30)22(20)21/h6-12,15-22H,13H2,1-5H3/b8-6-,9-7+/t15-,16-,17+,18+,19-,20+,21-,22-/m1/s1
InChI Key RQYZFUUTQJMTMJ-JCSZEPHKSA-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/)
Bioactivity Comments
The MIC for antibacterial activity in vitro against a panel of Clostridioides difficile strains is in the range of 0.4-1.6 μg/ml [1].
In Plasmodium falciparum, chlorotonil A has activity against all blood stages of the parasite lifecycle (see table below) [3].
Whole organism assay data
Key to terms and symbols Click on species/strain names for details Click column headers to sort
MOA/likely target Sp. Assay description Type Action Value Parameter Concentration range (M) Reference
Unknown MOA Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 Parasite growth inhibition assay - - 8.0 pIC50 - 3
⤷ pIC50 8.0 (IC50 9.1x10-9 M) [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA PfDd2

Plasmodium falciparum Dd2

P. falciparum strain Dd2 (PfDd2) is a clone derived from PfW2, following continuous culture in mefloquine. PfW2 was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy.
PfDd2 can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, pyrimethamine and mefloquine.
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 Parasite growth inhibition assay - - 7.7 pIC50 - 3
⤷ pIC50 7.7 (IC50 1.81x10-8 M) [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Unknown MOA Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 Parasite late stage (IV–V) gametocyte assay - - 7.5 pIC50 - 3
⤷ pIC50 7.5 (IC50 2.96x10-8 M) using an in vitro bioluminescence assay [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)