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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
SaltsNot Available
Brand namesNot Available
Brand mixturesNot 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[12.3.1.0^{3,11}.0^{4,9}]octadeca-3(11),4,6,8-tetraen-12-yl]-7-methoxy-3,13-diazapentacyclo[13.3.1.0^{2,10}.0^{4,9}.0^{13,18}]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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassNot Available
SubclassNot Available
Direct parentAlkaloids and Derivatives
Alternative parentsVobasan Alkaloids; Ibogan-type Alkaloids; Pyrroloazepines; Indoles; Piperidinecarboxylic Acids; Anisoles; Alkyl Aryl Ethers; Azepines; Dicarboxylic Acids and Derivatives; Pyrroles; Carboxylic Acid Esters; Tertiary Amines; Enolates; Polyamines
Substituentsalkyl aryl ether; azepine; dicarboxylic acid derivative; benzene; piperidine; pyrrole; tertiary amine; carboxylic acid ester; polyamine; ether; enolate; carboxylic acid derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
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
Property Value Probability
Human Intestinal Absorption + 0.9928
Blood Brain Barrier - 0.5295
Caco-2 permeable + 0.5
P-glycoprotein substrate Substrate 0.9264
P-glycoprotein inhibitor I Inhibitor 0.8829
P-glycoprotein inhibitor II Inhibitor 0.8026
Renal organic cation transporter Non-inhibitor 0.5461
CYP450 2C9 substrate Non-substrate 0.8491
CYP450 2D6 substrate Non-substrate 0.5836
CYP450 3A4 substrate Substrate 0.7867
CYP450 1A2 substrate Non-inhibitor 0.7083
CYP450 2C9 substrate Non-inhibitor 0.6209
CYP450 2D6 substrate Non-inhibitor 0.8255
CYP450 2C19 substrate Non-inhibitor 0.7443
CYP450 3A4 substrate Inhibitor 0.7262
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5987
Ames test Non AMES toxic 0.7269
Carcinogenicity Non-carcinogens 0.9345
Biodegradation Not ready biodegradable 0.9943
Rat acute toxicity 2.9345 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8902
hERG inhibition (predictor II) Inhibitor 0.6025
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
water solubility3.23e-03 g/lALOGPS
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 area99.89ChemAxon
rotatable bond count7ChemAxon
refractivity203.68ChemAxon
number of rings9ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
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
ResourceLink
KEGG CompoundC09252
PubChem Compound11953931
PubChem Substance99443228
ChemSpider10128230
PharmGKBPA165958347
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