5956-39-8

Usage

Uses

Used in Pharmaceutical Industry:
Epipolygodial is used as an anticancer agent for targeting drug-resistant cancer cells and other proliferative diseases. Its effectiveness against these diseases is attributed to its ability to disrupt cellular processes and inhibit the growth of cancerous cells, making it a promising compound for further research and development in the field of oncology.
Used in Other Industries:
While the primary focus of epipolygodial's applications is within the pharmaceutical industry, its unique chemical properties may also make it suitable for other industries, such as agriculture or chemical manufacturing. However, more research would be needed to determine its potential uses and benefits in these areas.

InChI:InChI=1/C15H22O2/c1-14(2)7-4-8-15(3)12(10-17)11(9-16)5-6-13(14)15/h9-10,13H,4-8H2,1-3H3/t13?,15-/m0/s1

Upstream product

• 83630-99-3 pu'ulenal 
• 22567-27-7 ((1S,4aR,8aS)-2-Hydroxymethyl-5,5,8a-trimethyl-1,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl)-methanol 
• 71557-96-5 dimethyl 3,5,6,7,8,8a-hexahydro-5,5,8a-trimethylnaphthalene-1,2-dicarboxylate 
• 5956-39-8 (1S,4aR,8aS)-5,5,8a-Trimethyl-1,4,4a,5,6,7,8,8a-octahydro-naphthalene-1,2-dicarbaldehyde 
• 361544-76-5 5,5,8a-Trimethyl-1,5,6,7,8,8a-hexahydro-naphthalene-1,2-dicarboxylic acid dimethyl ester 
• 71558-02-6 Dimethoxy carbonyl-1,2 trimethyl-5,5,8a Octahydro-1,4,4a,5,6,7,8,8a naphtalene-(1RS, 4aSR, 8aRS) 
• 6754-20-7 Polygodial 
• 79679-67-7 (S)-5,5,8a-Trimethyl-1,5,6,7,8,8a-hexahydro-naphthalene-1,2-dicarboxylic acid dimethyl ester 
• 71558-02-6 (1S,4aS)-5,5,8a-Trimethyl-1,4,4a,5,6,7,8,8a-octahydro-naphthalene-1,2-dicarboxylic acid dimethyl ester 

Downstream Products

• 5956-39-8 (1R,4aR,8aS)-5,5,8a-Trimethyl-1,4,4a,5,6,7,8,8a-octahydro-naphthalene-1,2-dicarbaldehyde 
• 16892-20-9 (4aS,8aR)-3,4,4a,5,6,7,8,8a-octahydro-5,5,8a-trimethyl-2(1H)-naphthalenone 

Relevant academic research and scientific papers

Structure-Pungency Relationships and TRP Channel Activation of Drimane Sesquiterpenes in Tasmanian Pepper (Tasmannia lanceolata)

Sensory-guided fractionation of extracts of Tasmanian pepper berries revealed 20 drimane sesquiterpens, among which polygodial, warburganal, and 1β-acetoxy-9-deoxy-isomuzigadial exhibited the lowest pungency threshold concentrations on the tongue surface (0.6-2.8 nmol/cm2) and elicited a dose-dependent calcium influx into mTRPA1 expressing CHO cells with the lowest EC50 values (4.5 ± 1.0 to 16.7 ± 7.5 μmol/L) and a good correlation to oral pungency thresholds (R2 = 0.986, linear regression). Calcium imaging assays demonstrated these chemosensates to induce a calcium influx into cultured trigeminal neurons prepared from wildtype (TRPA1+/+) mice, whereas no calcium influx was observed in neurons from TRPA1 knockout mice (TRPA1-/-), thus confirming the α,β-unsaturated 1,4-dialdehyde structure to be the required structural motif for a low oral puncency thresholds and activation of the Transient Receptor Potential Channel A1 (TRPA1). Time-resolved NMR experiments confirmed the pungency mediating mechanism for electrophilic drimane sesquiterpene dialdehydes to be different from that found for other electrophilic pungent agents like isothiocyanates, which have been shown to undergo a covalent binding with cysteine residues in TRPA1. Instead, the high-impact chemosensates polygodial, warburganal, and 1β-acetoxy-9-deoxy-isomuzigadial showed immediate reactivity with the ?-amino group of lysine side chains to give pyrrole-type conjugates, thus showing evidence for TRPA1 activation by covalent lysine modification.

Effect of polygodial and its direct derivatives on the mammalian Na+/K+-ATPase activity

The sesquiterpene polygodial is an agonist of the transient receptor potential vanilloid 1 (TRPV1). Our group recently reported the synthesis and anticancer effects of polygodial and its derivatives, and showed that these compounds retain activity against apoptosis- and multidrug-resistant cancer cells. Herein, we tested the inhibitory effect of these compounds on the activity of the enzyme Na+/K+-ATPase (NKA) from kidney (α1 isoform) and brain (α2 and α3 isoforms) guinea pig extracts. Polygodial (1) displayed a dose-dependent inhibition of both kidney and brain purified NKA preparations, with higher sensitivity for the cerebral isoforms. Polygo-11,12-diol (2) and C11,C12-pyridazine derivative (3) proved to be poor inhibitors. Unsaturated ester (4) and 9-epipolygodial (5) inhibited NKA preparations from brain and kidney, with the same inhibitory potency. Nevertheless, they did not achieve maximum inhibition even at higher concentration. Comparing the inhibitory potency in crude homogenates and purified preparations of NKA, compounds 4 and 5 revealed a degree of selectivity toward the renal enzyme. Kinetic studies showed a non-competitive inhibition for Na+ and K+ by compounds 1, 4 and 5 and for ATP by 1 and 4. However, compound 5 presented a competitive inhibition type. Furthermore, K+-activated p-nitrophenylphosphatase activity of these purified preparations was not inhibited by 1, 4 and 5, suggesting that these compounds acted in the initial phase of the enzyme's catalytic cycle. These findings suggest that the antitumor action of polygodial and its analogues may be linked to their NKA inhibitory properties and reinforce that NKA may be an important target for cancer therapy.

DEFENSE ALLOMONES OF SOME MARINE MOLLUSKS

Certain marine mollusks that lack obvious physical protection have evolved various biological and chemical defense strategies.One type of chemical defense involves accumulation of small organic molecules largely from the diet, which afford protection from common predators.Our work and research by others has shown that the animals can utilize different structural types.Interestingly several of the defense allomones which have been defined are structurally related to the drimane sesquiterpenoids which have been shown to be antifeedants against terrestrial insects.

Polygodial analog induces apoptosis in LNCaP prostate cancer cells

Prostate cancer (PCa) is the second leading cause of death in American men. The chemotherapeutic treatment strategies are generally not effective and can lead to side effects. Hence, there is an urgent need to identify novel chemotherapeutic agents. The aim of this study was to synthesize and evaluate the therapeutic effects of a synthetic analog of polygodial (PG), a pungent constituent abundantly present in mountain pepper, water pepper and dorrigo pepper, on LNCaP PCa cell line and its anti-cancer mechanisms in a preclinical study. We evaluated the anti-cancer potential of the PG analog namely DRP-27 using various assays such as cell viability by MTT assay, anchorage independent growth by soft agar assay, reactive oxygen species generation by 2′,7′-dichlorofluorescein probe-based fluorescence assay, and apoptosis by Annexin-V and TUNEL assays respectively. Western blot analysis was performed to identify the molecular mechanism of DRP-27-induced cell death. Our results showed that DRP-27 significantly inhibited LNCaP cell proliferation in a dose-dependent manner at 48 h treatment in vitro. In addition, DRP-27 potently inhibited anchorage-independent growth of these cells. Flow cytometry, Annexin-V and TUNEL assays confirmed that DRP-27 induces apoptosis in LNCaP cells. DRP-27 also induced the activation of intracellular reactive oxygen species. Western blot analysis revealed that DRP-27 downregulated the expression of survivin, while activating Bax and DNA damage marker pH2AX in LNCaP cells. In conclusion, our study suggests that DRP-27 might be an effective anti-cancer agent for PCa.

Activity of natural and synthetic polygodial derivatives against Trypanosoma cruzi amastigotes, trypomastigotes and epimastigotes

Our laboratories have been investigating biological effects of a sesquiterpenoid polygodial and its natural and synthetic analogues. Herein, we report the evaluation of these compounds against the three forms of Trypanosoma cruzi, amastigotes, trypomastigotes and epimastigotes. Although polygodial was found to be poorly active, its natural congener epipolygodial and synthetic Wittig-derived analogues showed low micromolar potency against all three forms of the parasite. Synthetic α,β-unsaturated phosphonate 9 compared favorably with clinically approved drugs benznidazole and nifurtimox, and was effective against trypomastigotes, toward which benznidazole showed no activity. (Figure presented.).

Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9-Epipolygodial against Drug-Resistant Cancer Cells

Polygodial, a terpenoid dialdehyde isolated from Polygonum hydropiper L., is a known agonist of the transient receptor potential vanilloid 1 (TRPV1). In this investigation a series of polygodial analogues were prepared and investigated for TRPV1-agonist and anticancer activities. These experiments led to the identification of 9-epipolygodial, which has antiproliferative potency significantly exceeding that of polygodial. 9-Epipolygodial was found to maintain potency against apoptosis-resistant cancer cells as well as those displaying the multidrug-resistant (MDR) phenotype. In addition, the chemical feasibility for the previously proposed mechanism of action of polygodial, involving the formation of a Paal-Knorr pyrrole with a lysine residue on the target protein, was demonstrated by the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. These compounds should inspire further work in this area aimed at the development of new pharmacological agents, or the exploration of novel mechanisms of covalent modification of biological molecules with natural products.

Probing the Structure-Activity Relationship of the Natural Antifouling Agent Polygodial against both Micro- and Macrofoulers by Semisynthetic Modification

The current study represents the first comprehensive investigation into the general antifouling activities of the natural drimane sesquiterpene polygodial. Previous studies have highlighted a high antifouling effect toward macrofoulers, such as ascidians, tubeworms, and mussels, but no reports about the general antifouling effect of polygodial have been communicated before. To probe the structural and chemical basis for antifouling activity, a library of 11 polygodial analogues was prepared by semisynthesis. The library was designed to yield derivatives with ranging polarities and the ability to engage in both covalent and noncovalent interactions, while still remaining within the drimane sesquiterpene scaffold. The prepared compounds were screened against 14 relevant marine micro- and macrofouling species. Several of the polygodial analogues displayed inhibitory activities at sub-microgram/mL concentrations. These antifouling effects were most pronounced against the macrofouling ascidian Ciona savignyi and the barnacle Balanus improvisus, with inhibitory activities observed for selected compounds comparable or superior to several commercial antifouling products. The inhibitory activity against the microfouling bacteria and microalgae was reversible and significantly less pronounced than for the macrofoulers. This study illustrates that the macro- and microfoulers are targeted by the compounds via different mechanisms.

Partial Synthesis of ( - )-11,12-Dinordriman-8-one and the ( - )-Enantiomer of Polywood

A chiral sequiterpene diol 6, readily available from the natural product polygodial (4), has been used for the first partial synthesis of the title compounds.

Synthesis of all possible stereoisomers of polygodial

The three possible isomers of polygodial, epimers at C-9, cis and trans fused, are described.Controlled kinetic and thermodynamic epimerizations allow preparation of all stereoisomers from the same key intermediate.

EFFICIENT TOTAL SYNTHESES OF POLYGODIAL AND DRIMENIN.

A short and stereoselective total synthesis of (+/-) polygodial and drimenin is presented.The efficiency of the synthesis is due to the easy access to intermediate diol 4 and its successful direct oxidation into polygodial.