Amorfrutin C

Amorfrutin C at a Glance

Amorfrutin C is a prenylated benzoic acid of the amorfrutin class, carrying two prenyl groups where amorfrutin A carries one. It was described as a new natural product in 2016, isolated from the roots of the wild licorice Glycyrrhiza foetida in the same study that characterised its biology ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}.

It is the family’s odd member. The amorfrutins are known as selective PPARγ agonists — the dietary molecules that reproduce a glitazone’s metabolic benefit in mice without the fat gain ^{2Reference 2Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →}. Amorfrutin C activates PPAR comparatively weakly ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}. What it does instead is disrupt mitochondria: it depolarises the mitochondrial membrane at an IC50 of 0.6 µM, forces permanent opening of the permeability transition pore, and kills colorectal, prostate and breast cancer cells at IC50 values of 8–16 µM ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}.

The paper that describes it calls it a promising lead for anticancer drug development. Ten years on, that is still all there is: one primary study, one synthesis, and no animal work of any kind.

It Comes From Licorice, Not From Amorpha

This molecule sits in the false indigo bush’s compound list because it belongs to the amorfrutin family, which the shrub gave its name to. The chemistry does not follow the name.

Amorfrutin C was isolated from Glycyrrhiza foetida roots, and every subsequent study of it has used licorice-sourced or synthetic material ^{1,4,7Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →Reference 4Fujita T et al. · 2022In vitroSynthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells — in vitroView study →Reference 7Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →}. There is no published report of it in Amorpha fruticosa. When the amorfrutins of A. fruticosa fruit were quantified by validated HPLC, the compounds present and measurable were amorfrutin A, amorfrutin B and 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl — amorfrutin C was not among them, and no amorfrutin at all was detected in Amorpha canescens or in the roots of the three commercial licorice species G. glabra, G. uralensis and G. inflata ^{5Reference 5Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}.

There is also a naming trap worth knowing about. In the mass-spectrometry literature on A. fruticosa, 2-carboxy-3,5-dihydroxy-4-geranylbibenzyl is abbreviated “AC” to sit alongside AA and AB for amorfrutins A and B ^{6Reference 6Chen C et al. · 2018Neutral Loss Scan - Based Strategy for Integrated Identification of Amorfrutin Derivatives, New Peroxisome Proliferator-Activated Receptor Gamma Agonists, from Amorpha Fruticosa by UPLC-QqQ-MS/MS and UPLC-Q-TOF-MSView study →}. That abbreviation is not amorfrutin C, and the two are different molecules with different substitution.

The practical reading: amorfrutin C is a licorice-derived compound of the amorfrutin scaffold, not a false-indigo-bush constituent, and no preparation of either plant is known to deliver it.

What It's Used For

One primary study carries essentially the whole file, and it is a thorough one — cell-cycle analysis, apoptosis markers, mitochondrial function, structure–activity work and synergy testing, all in cell culture ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}.

Evidence by IndicationStrength of support · Beta

01Antiproliferative Activity via Mitochondrial DisruptionShaky26%One thorough in-vitro study across four cancer lines plus a synthetic-material replication in a fifth ^{1,4Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →Reference 4Fujita T et al. · 2022In vitroSynthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells — in vitroView study →}

02PPAR ActivationShaky16%Reported as comparatively weak in the study that described the molecule; the family’s metabolic evidence belongs to its siblings ^{1,2,7Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →Reference 2Weidner C et al. · 2012AnimalAmorfrutins are potent antidiabetic dietary natural products — animal study in miceView study →Reference 7Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →}

Mechanisms

The decarboxylated analogue of amorfrutin A is also cytotoxic while losing PPAR agonism ^{7Reference 7Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →} — consistent with the two activities in this family being separable, and with amorfrutin C sitting on the cytotoxic side of that split.

Pharmacokinetics

None. No absorption, distribution, metabolism, half-life or bioavailability data exist for amorfrutin C in any species, and no in-vivo study of any kind has been published.

Clinical Trials

None, and none preceded by animal work.

Last checked: September 2026.

Isolate vs. Plant Studies

Entirely isolate, with no plant-side evidence at all — and in this case that is not a caveat about transferability but about relevance. The material tested was purified from Glycyrrhiza foetida roots or made synthetically ^{1,4Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →Reference 4Fujita T et al. · 2022In vitroSynthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells — in vitroView study →}. No extract of any plant has been shown to deliver amorfrutin C, no traditional or commercial preparation contains a known amount of it, and the plant most often named in connection with the amorfrutins has never been reported to contain this one ^{5Reference 5Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}. The molecule exists in the literature as a chemical entity rather than as a plant constituent anyone consumes.

Prevalence in Nature

Amorfrutin C has been reported from a single source: the roots of Glycyrrhiza foetida, a wild licorice of the Mediterranean and North Africa, where it occurs alongside amorfrutin B ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}. The species’ aerial parts carry a wider amorfrutin series still — six new and six known members were characterised in one 2023 analysis, together with alkyl-type phytocannabinoids ^{7Reference 7Serino E et al. · 2023In vitroPPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitroView study →}, and ten amorfrutins from the same plant were available in purified form for an antibacterial screen ^{8Reference 8Lucidi M et al. · 2026In vitroAmorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of actionView study →}.

No quantitative content figure has been published for amorfrutin C in any tissue, and it has not been detected in the Amorpha material where the family’s quantitative work has been done ^{5Reference 5Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}. Its distribution beyond G. foetida is simply unknown rather than established as absent — few plants have been looked at with a method that would find it.

Discovery & Synthesis

Amorfrutin C entered the literature in 2016 as compound 2 of a two-compound isolation from Glycyrrhiza foetida roots: a structurally related new natural product beside the already-known amorfrutin B, characterised and biologically profiled in the same paper ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}.

Synthesis followed in 2019. A unified route made both amorfrutin A and amorfrutin C from commercially available 3,5-dimethoxybenzaldehyde; the key step for amorfrutin C is a double Claisen rearrangement of a di-O-(1,1-dimethylallyl)resorcinol derivative, which installs both prenyl groups at C3 and C5 in one operation. It took ten steps at 10% overall yield — noticeably harder than the nine steps and 38% that the mono-prenylated amorfrutin A required ^{3Reference 3Fujita T et al. · 2019Unified total synthesis of amorfrutins A and C via the Claisen rearrangementView study →}. A later synthetic campaign prepared amorfrutins A–D for cytotoxicity testing against pancreatic carcinoma cells ^{4Reference 4Fujita T et al. · 2022In vitroSynthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells — in vitroView study →}.

There is no commercial production and no extraction industry. Amorfrutin C is a research chemical.

Patents: not yet researched.

Toxicity & Safety

The flag here reads moderate for a compound with no toxicology at all, on the strength of its measured mechanism.

Safety at a Glance

⚠️ Moderate toxicity

• Mitochondrial poison at sub-micromolar concentration. Membrane depolarisation at IC50 0.6 µM and permanent permeability-transition-pore opening are effects on an organelle every cell depends on, not a tumour-specific target ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}.
• The cancer-cell data are not a therapeutic index. Reduced potency against primary colon cells is one comparison in one experiment; no normal-tissue panel and no animal study exist ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}.
• No toxicology of any kind. No acute, repeat-dose, genotoxicity, reproductive or developmental study, in any species.
• Not a licorice constituent in the everyday sense. Nothing about this molecule transfers to commercial licorice, which contains no amorfrutins ^{5Reference 5Chen C et al. · 2016Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLCView study →}.

Full Safety & Interactions Detail

What is measured. Amorfrutin C depolarises mitochondrial membranes at IC50 0.6 µM, permanently opens the permeability transition pore, raises mitochondrial oxygen consumption and extracellular acidification, and induces caspase-dependent apoptosis with ROS generation in cancer cell lines at 8–16 µM. It was reported as less potent in primary colon cells, which is the only selectivity observation available ^{1Reference 1Weidner C et al. · 2016In vitroAmorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitroView study →}.

What is not. There is no in-vivo exposure of any kind — no acute toxicity study, no repeat-dose work, no genotoxicity assay, no reproductive or developmental data, and no pharmacokinetics. Nothing supports a statement about safety in a whole organism, in either direction.

Interactions. No cytochrome-P450, transporter or drug-interaction data exist. The family’s PPAR activity would raise a pharmacodynamic question with glucose-lowering drugs, but amorfrutin C is the weak PPAR member, so even that inference is thin.

Reproductive note. No reproductive or developmental data exist for the isolated molecule.

Dosage

There is no dose, in any sense that applies to a person. Amorfrutin C has been added to cell cultures and to nothing else. The concentrations on record:

These are laboratory concentrations, not a personal recommendation, and no plant preparation is known to supply this molecule.

References

1. Weidner C, Rousseau M, Micikas RJ, et al. (2016). Amorfrutin C Induces Apoptosis and Inhibits Proliferation in Colon Cancer Cells through Targeting Mitochondria — in vitro. J Nat Prod. https://pubmed.ncbi.nlm.nih.gov/26731300/
2. Weidner C, de Groot JC, Prasad A, et al. (2012). Amorfrutins are potent antidiabetic dietary natural products — animal study in mice. Proc Natl Acad Sci U S A. https://pubmed.ncbi.nlm.nih.gov/22509006/
3. Fujita T, Kuwahara S, Ogura Y (2019). Unified total synthesis of amorfrutins A and C via the Claisen rearrangement. Biosci Biotechnol Biochem. https://pubmed.ncbi.nlm.nih.gov/31130067/
4. Fujita T, Lin J, Kimishima A, et al. (2022). Synthesis and biological evaluation of cajaninstilbene acid and amorfrutins A-D as cytotoxic agents against human pancreatic carcinoma PANC-1 cells — in vitro. Biosci Biotechnol Biochem. https://pubmed.ncbi.nlm.nih.gov/35157035/
5. Chen C, Wu Y, Du L (2016). Qualitative and quantitative analysis of amorfrutins, novel antidiabetic dietary natural products, by HPLC. Pharm Biol. https://pubmed.ncbi.nlm.nih.gov/26004584/
6. Chen C, Xue Y, Li QM, et al. (2018). Neutral Loss Scan - Based Strategy for Integrated Identification of Amorfrutin Derivatives, New Peroxisome Proliferator-Activated Receptor Gamma Agonists, from Amorpha Fruticosa by UPLC-QqQ-MS/MS and UPLC-Q-TOF-MS. J Am Soc Mass Spectrom. https://pubmed.ncbi.nlm.nih.gov/29404969/
7. Serino E, Iannotti FA, Al-Hmadi HB, et al. (2023). PPARα/γ-Targeting Amorfrutin Phytocannabinoids from Aerial Parts of Glycyrrhiza foetida — in vitro. J Nat Prod. https://pubmed.ncbi.nlm.nih.gov/37940359/
8. Lucidi M, Imperi F, Turi M, et al. (2026). Amorfrutin-A, a membrane-targeting phytochemical active against multidrug-resistant Staphylococcus aureus: In vitro and in vivo activity and mechanism of action. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/42235358/

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