Voacamine

Identification

Name
Voacamine
Accession Number
DB04877
Type
Small Molecule
Groups
Approved, 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
  • Methyl-12-methoxy-13-(17-methoxy-17-oxovobasan-3alpha-yl)ibogamine-18-carboxylate
  • Voacanginine
  • Vocamine
Categories
UNII
2Z504YT5AG
CAS number
3371-85-5
Weight
Average: 704.8968
Monoisotopic: 704.393770794
Chemical Formula
C43H52N4O5
InChI Key
VCMIRXRRQJNZJT-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][[email protected]@]12C[[email protected]](CC)[[email protected]]3([H])N(C1)CCC1=C(NC4=CC(=C(OC)C=C14)[[email protected]@]1([H])C[[email protected]]4([H])C(C(=O)OC)[[email protected]@]([H])(CC5=C1NC1=CC=CC=C51)N(C)C\C4=C\C)[[email protected]@]3(C2)C(=O)OC

Pharmacology

Indication

For the treatment of malaria. Also under investigation for the modulation of multidrug resistance in cancer cells.

Structured Indications
Not Available
Pharmacodynamics

Voacamine 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 action

Voacamine 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.

TargetActionsOrganism
UMultidrug resistance protein 1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Plasmodium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General 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:16273216 ]
  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:17070665 ]
  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:14612920 ]
External Links
Human Metabolome Database
HMDB15597
KEGG Compound
C09252
PubChem Compound
11953931
PubChem Substance
99443228
ChemSpider
10128230
ChEMBL
CHEMBL445022
PharmGKB
PA165958347
ATC Codes
Not Available
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Not Available
MSDS
Not Available

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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 inhibitorNon-inhibitor0.6209
CYP450 2D6 inhibitorNon-inhibitor0.8255
CYP450 2C19 inhibitorNon-inhibitor0.7443
CYP450 3A4 inhibitorInhibitor0.7262
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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of chemical entities 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.
Kingdom
Chemical entities
Super Class
Organic compounds
Class
Alkaloids and derivatives
Sub Class
Ibogan-type alkaloids
Direct Parent
Ibogan-type alkaloids
Alternative Parents
Vobasan alkaloids / 3-alkylindoles / Pyrroloazepines / Piperidinecarboxylic acids / Anisoles / Alkyl aryl ethers / Aralkylamines / Azepines / Dicarboxylic acids and derivatives / Pyrroles
show 9 more
Substituents
Ibogan skeleton / Vobasan skeleton / Catharanthine skeleton / Pyrroloazepine / 3-alkylindole / Indole / Indole or derivatives / Piperidinecarboxylic acid / Anisole / Alkyl aryl ether
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:16273216 ]
  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:14612920 ]

Drug created on October 20, 2007 10:45 / Updated on October 02, 2017 05:39