Voacamine

Identification

Generic Name
Voacamine
DrugBank Accession Number
DB04877
Background

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.

Type
Small Molecule
Groups
Experimental
Structure
Weight
Average: 704.8968
Monoisotopic: 704.393770794
Chemical Formula
C43H52N4O5
Synonyms
  • Methyl 12-methoxy-13-(17-methoxy-17-oxovobasan-3alpha-yl)ibogamine-18-carboxylate
  • Voacanginine
  • Vocamine
External IDs
  • MMH-18

Pharmacology

Indication

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

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Contraindications & Blackbox Warnings
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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
UP-glycoprotein 1
inhibitor
Humans
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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Ibogan-type alkaloids
Sub Class
Not Available
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
3-alkylindole / Alkyl aryl ether / Amine / Amino acid or derivatives / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Azepine / Benzenoid
show 26 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Plasmodium

Chemical Identifiers

UNII
2Z504YT5AG
CAS number
3371-85-5
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[12.3.1.0^{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

References

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. [Article]
  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. [Article]
  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. [Article]
Human Metabolome Database
HMDB0015597
KEGG Compound
C09252
PubChem Compound
11953931
PubChem Substance
99443228
ChemSpider
10128230
ChEMBL
CHEMBL445022
PharmGKB
PA165958347
Wikipedia
Voacamine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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
Polarizability44.36 Å3Chemaxon
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/MSsplash10-0a4i-0000000900-5f8c46b2362ea5a68c7b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0fk9-0000009400-64ff7d676da626e47176
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0000004900-a25fd95381fd5d37cdfa
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0uk9-0001009700-7e1472d07e18fca0c8f1
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-053j-0105198200-af6152426f54c5646d30
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009001100-da174a76518aa4336907
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-283.7600277
predicted
DarkChem Lite v0.1.0
[M-H]-269.8898
predicted
DeepCCS 1.0 (2019)
[M+H]+282.8867277
predicted
DarkChem Lite v0.1.0
[M+H]+271.61356
predicted
DeepCCS 1.0 (2019)
[M+Na]+284.3140277
predicted
DarkChem Lite v0.1.0
[M+Na]+277.94308
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
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. [Article]
  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. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
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. [Article]

Drug created at October 20, 2007 16:45 / Updated at June 12, 2020 16:52