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Identification
NameVoacamine
Accession NumberDB04877
TypeSmall Molecule
GroupsApproved, Investigational
Description

Voacamine is an alkaloid isolated from the bark of the Pescheria fuchsiae folia tree. It is an antimalarial drug approved for use in several African countries. Voacamine is also under investigation for use in modulating multidrug-resistance in tumor cells.

Structure
Thumb
Synonyms
SynonymLanguageCode
Methyl-12-methoxy-13-(17-methoxy-17-oxovobasan-3alpha-yl)ibogamine-18-carboxylateNot AvailableNot Available
VoacanginineNot AvailableNot Available
VocamineNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number3371-85-5
WeightAverage: 704.8968
Monoisotopic: 704.393770794
Chemical FormulaC43H52N4O5
InChI KeyVCMIRXRRQJNZJT-XRMSBCOFSA-N
InChI
InChI=1S/C43H52N4O5/c1-7-24-15-23-20-43(42(49)52-6)39-27(13-14-47(21-23)40(24)43)29-19-36(50-4)30(17-34(29)45-39)31-16-28-25(8-2)22-46(3)35(37(28)41(48)51-5)18-32-26-11-9-10-12-33(26)44-38(31)32/h8-12,17,19,23-24,28,31,35,37,40,44-45H,7,13-16,18,20-22H2,1-6H3/b25-8-/t23-,24-,28-,31+,35+,37?,40-,43+/m0/s1
IUPAC Name
methyl (1S,15S,17S,18S)-17-ethyl-6-[(1R,12R,14R,15E)-15-ethylidene-18-(methoxycarbonyl)-17-methyl-10,17-diazatetracyclo[12.3.1.0³,¹¹.0⁴,⁹]octadeca-3(11),4,6,8-tetraen-12-yl]-7-methoxy-3,13-diazapentacyclo[13.3.1.0²,¹⁰.0⁴,⁹.0¹³,¹⁸]nonadeca-2(10),4,6,8-tetraene-1-carboxylate
SMILES
[H][C@@]12C[C@H](CC)[C@]3([H])N(C1)CCC1=C(NC4=CC(=C(OC)C=C14)[C@@]1([H])C[C@]4([H])C(C(=O)OC)[C@@]([H])(CC5=C1NC1=CC=CC=C51)N(C)C\C4=C\C)[C@@]3(C2)C(=O)OC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as ibogan-type alkaloids. These are indole alkaloids with a structure based on the ibogamine skeleton or a derivative thereof. Ibogamine is a pentacyclic heterocyclic compound consisting of an indole fused to an azepane-containing tricyclic moiety ring. Iboga alkaloids arise from the cyclization of a secodine-type precursor through the formation of a 16,21 bond.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassIbogan-type alkaloids
Sub ClassNot Available
Direct ParentIbogan-type alkaloids
Alternative Parents
Substituents
  • Ibogan skeleton
  • Vobasan skeleton
  • Catharanthine skeleton
  • Hydroxyindole
  • Pyrroloazepine
  • Piperidinecarboxylic acid
  • Indole or derivatives
  • Indole
  • Anisole
  • Aralkylamine
  • Azepine
  • Alkyl aryl ether
  • Benzenoid
  • Piperidine
  • Dicarboxylic acid or derivatives
  • Heteroaromatic compound
  • Methyl ester
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of malaria. Also under investigation for the modulation of multidrug resistance in cancer cells.
PharmacodynamicsVoacamine is an anti-malarial extracted from the Brazilian tree Peschiera fuchsiaefolia. In one study (PMID: 11180519), the in vivo antiplasmodial activity of voacamine was assessed in a 4-day test. It was shown to exhibit in vivo activity with 25.4% and 43.4% inhibition of parasitaemia with 2.5 and 10 mg/kg, respectively. In synchronized cultures, it was found to act on trophozoite and schizont stages of Plasmodium falciparum. Voacamine is a bisindolic alkaloid under investigation for modulation of multidrug resistance to enhance anticancer drugs such as doxorubicin.
Mechanism of actionVoacamine is possibly a substrate for P-glycoprotein (P-gp), an efflux pump responsible for multidrug resistance in tumor cells. Voacamine may compete with anticancer drugs such as doxorubicin for P-gp transport, decreasing removal of doxorubicin.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Plasmodium
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9928
Blood Brain Barrier-0.5295
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.9264
P-glycoprotein inhibitor IInhibitor0.8829
P-glycoprotein inhibitor IIInhibitor0.8026
Renal organic cation transporterNon-inhibitor0.5461
CYP450 2C9 substrateNon-substrate0.8491
CYP450 2D6 substrateNon-substrate0.5836
CYP450 3A4 substrateSubstrate0.7867
CYP450 1A2 substrateNon-inhibitor0.7083
CYP450 2C9 substrateNon-inhibitor0.6209
CYP450 2D6 substrateNon-inhibitor0.8255
CYP450 2C19 substrateNon-inhibitor0.7443
CYP450 3A4 substrateInhibitor0.7262
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5987
Ames testNon AMES toxic0.7269
CarcinogenicityNon-carcinogens0.9345
BiodegradationNot ready biodegradable0.9943
Rat acute toxicity2.9345 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8902
hERG inhibition (predictor II)Inhibitor0.6025
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00323 mg/mLALOGPS
logP6.26ALOGPS
logP6.21ChemAxon
logS-5.3ALOGPS
pKa (Strongest Acidic)15.56ChemAxon
pKa (Strongest Basic)8.53ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.89 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity203.68 m3·mol-1ChemAxon
Number of Rings9ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Meschini S, Marra M, Condello M, Calcabrini A, Federici E, Dupuis ML, Cianfriglia M, Arancia G: Voacamine, an alkaloid extracted from Peschiera fuchsiaefolia, inhibits P-glycoprotein action in multidrug-resistant tumor cells. Int J Oncol. 2005 Dec;27(6):1597-603. Pubmed
  2. Meschini S, Condello M, Marra M, Formisano G, Federici E, Arancia G: Autophagy-mediated chemosensitizing effect of the plant alkaloid voacamine on multidrug resistant cells. Toxicol In Vitro. 2007 Mar;21(2):197-203. Epub 2006 Sep 16. Pubmed
  3. Meschini S, Marra M, Calcabrini A, Federici E, Galeffi C, Arancia G: Voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells. Int J Oncol. 2003 Dec;23(6):1505-13. Pubmed
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor, competitive

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Meschini S, Marra M, Condello M, Calcabrini A, Federici E, Dupuis ML, Cianfriglia M, Arancia G: Voacamine, an alkaloid extracted from Peschiera fuchsiaefolia, inhibits P-glycoprotein action in multidrug-resistant tumor cells. Int J Oncol. 2005 Dec;27(6):1597-603. Pubmed
  2. Meschini S, Marra M, Calcabrini A, Federici E, Galeffi C, Arancia G: Voacamine, a bisindolic alkaloid from Peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells. Int J Oncol. 2003 Dec;23(6):1505-13. Pubmed

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Drug created on October 20, 2007 10:45 / Updated on September 16, 2013 17:26