PTP1B Inhibitory Activity Research Articles

Anti-diabetic potential of Viburnum betulifolium fruits: Sesquilignans with α-amylase, α-glucosidase, and PTP1B inhibitory activities

Viburnum betulifolium Batal. is an incredibly attractive and widely cultivated plant due to the great industrial value of its fruits, flowers, roots, stems, and barks. In this study, the MeOH extract of Viburnum betulifolium fruits (VBFM) was first reported to show obvious hypoglycemic effects in diabetic and normal mice, and it exhibited weak inhibitory effect on α-amylase and significant inhibition against α-glucosidase and PTP1B. In order to elucidate the anti-diabetic components, six undescribed sesquilignans, vibetulifols A−F (1−6), one new natural sesquilignan 9, and three known analogues (7, 8, and 10) were isolated from VBFM by bioactivity-guided fractionation and identified by extensive spectroscopic analyses. Compounds 1−8 exhibited moderate inhibitory effects on α-amylase with IC50 values ranging from 35.10 to 51.52 μM, and compounds 1−3 and 6 displayed significant α-glucosidase inhibitory effects (IC50 = 5.17, 6.73, 3.05, and 15.37 μM, respectively), while compounds 3 and 4 also displayed potent PTP1B inhibitory activities (IC50 = 3.29 and 3.15 μM, respectively) and good selectivity over TCPTP. Furthermore, the enzyme kinetic studies and molecular modeling analyses for compounds 3 and 4 were also performed. These results could provide scientific guidance and foundation for the further development and utilization of V. betulifolium fruits in pharmaceutical industry.

A new polysaccharide from leaves of Sabia parviflora

A new polysaccharide (SPT1) was isolated from Sabia parviflora Wall. ex Roxb., and the structure was identified by GPC, 1D and 2D NMR spectroscopy, SEM and AFM. The results showed that the average molecular weight (Mn) of SPT1 was 4.057 × 103 Da, and it was composed of α-glucose with a connection mode of 1→6. The SEM showed that the particle size of SPT1 was 1–200 μm and there were small gaps between the crystals. SPT1 was mainly spherical aggregates in AFM, each aggregate was 0.550–0.983 μm long, 1.059–2.275 μm wide and 208–450 nm high. Furthermore, its liver-protective and PTP1B inhibitory activities were evaluated, and the results showed that SPT1 exhibited moderate effects of liver-protective and PTP1B inhibitory activity. The above results provided experimental evidence for the folk application of S. parviflora in the treatment of hepatitis.

Effects of p-Hydroxybenzaldehyde, Vanillin, and Syringaldehyde on Protein Tyrosine Phosphatase 1B Activity

Background: The PTP 1B is a negative regulator of insulin signal transduction and hence, serves as a therapeutic target in the treatment of diabetes. Objective: The present study investigated the inhibitory effects of p-hydroxybenzaldehyde, vanillin, and syringaldehyde on the activity of protein tyrosine phosphatases phosphatase 1B (PTP 1B) in vitro. Method: The PTP 1B inhibitory assay and mode of inhibition of the three compounds were determined using p-nitrophenyl phosphate (p-NPP) in a 96 well microplate. Molecular docking was used to predict the binding affinities of the compounds with the PTP 1B. Results: The results showed that syringaldehyde exhibited significantly (p< 0.05) higher PTP 1B inhibitory activity (IC50: 12.75 µM) compared to p-hydroxybenzaldehyde (IC50: 33.79 µM) and vanillin (IC50: 42.82 µM) as well as the standards suramin (IC50: 28.35 µM) and ursolic acid (IC50: 19.45 µM). Syringaldehyde and vanillin showed uncompetitive inhibition whereas, p-hydroxybenzaldehyde showed a mixed inhibition type. The molecular docking simulation predicted negative binding energies of -5.0 kcal/mol, -5.5 kcal/mol, and -5.5 kcal/mol for p-hydroxybenzaldehyde, vanillin, and syringaldehyde respectively. Conclusion: Syringaldehyde showed higher inhibition of PTP 1B compared to other phenolic aldehydes and could be the mechanism of its antidiabetic activity. Hence, further studies are warranted to confirm the efficacy and toxicity of the compound

Synthesis, characterization, biomolecular interaction and in vitro glucose metabolism studies of dioxidovanadium(V) benzimidazole compounds

We have previously reported that the metal-based anti-diabetic drug candidates, cis-[VO2(obz)py] (1) (Hobz = 2-hydroxyphenyl-1H-benzimidazole and py = pyridine) and cis-[VO2(Hpybz)(pybz)] (2) (Hpybz = 2-pyridyl-1H-benzimidazole) illustrated hypoglycaemic activities both in vitro and in vivo, respectively. Herein, we report the biomolecular interaction studies of 1 and 2 as well as their new analogues: cis-[VO2(Hmpybz)(mpybz)] (3) (Hmpybz = 2-(4-methyl-2-pyridyl-1H-benzimidazole) and cis-[VO2(mobz)py] (4) (Hombz = 2-(5–6 dimethyl-2-pyridine)-1H-benzimidazole) towards Bovine Serum Albumin (BSA) and Protein Phosphatase Tyrosine (PTP)-1B enzyme, respectively. The new metal complexes 3 and 4 were characterized with the aid of various characterization techniques and their structures were confirmed by single crystal X-ray crystallography and elemental analysis. Unique concentration-dependent PTP-1B inhibitory activities of 2 and 3 were observed under pre- and post-lysis experimental conditions. Lactate assays showed that 2 and 3 reduces the rate of lactate production. As there is a linear relationship between lactate levels and insulin resistance, this suggests that compounds 2 and 3 are able to alleviate this phenotype via the reduction of lactate build-up in HEK293T cells. The glucose consumption rate was insignificantly altered in response to 2 and 3, suggesting that these compounds do not affect glucose uptake in HEK293T cells.

Six Unusual Meroterpenoids from the Leaves of Psidium guajava L. and Their PTP1B Inhibitory Activities.

Six unusual meroterpenoids, psidiguajadiol A-J (1-6), and three known meroterpenoids (7-9) were isolated from the leaves of Psidium guajava L. Compounds 2-6 represent the first examples of 6/8-formyl-5,7-dihydroxy-4-phenylchromane-coupled sesquiterpenoids. The structures of the undescribed compounds, including their absolute configurations, were elucidated by spectroscopic analyses, X-ray diffraction, and computational calculations. Compounds 3, 4, and 6 exhibited inhibitory activities against PTP1B with IC50 values of 9.83, 18.52, and 16.87 μM, respectively. In light of these findings, we performed molecular docking studies to predict their inhibition mechanisms at the atomic level.

PTP1B and α-glucosidase inhibitory activities of the chemical constituents from Hedera rhombea fruits: Kinetic analysis and molecular docking simulation

In this study, we present the first investigation of Hedera rhombea Bean fruit, which led to the isolation of six undescribed compounds including two megastigmane glucosides, two rare 1,4-dioxane neolignanes, and two quinic acid derivatives, together with 26 known compounds. Their structures and absolute configurations were elucidated by extensive analysis of NMR spectroscopic data, HRMS, and ECD calculations. This is the first report on the isolation of methyl 3-O-caffeoyl-5-O-p-coumaroylquinate from a natural source. Among the isolated compounds, falcarindiol and caffeoyltryptophan showed significant PTP1B inhibition with IC50 values of 7.32 and 16.99 μM, respectively, compared to those of the positive controls [sodium orthovanadate (IC50 = 17.96 μM) and ursolic acid (IC50 = 4.53 μM)]. These two compounds along with several other compounds displayed significant α-glucosidase inhibitions with IC50 values ranging from 12.88 to 91.89 μM, stronger than that of the positive control (acarbose, IC50 = 298.07 μM). Enzyme kinetic analysis indicated that caffeoyltryptophan and falcarindiol displayed competitive and mixed-type PTP1B inhibition, respectively, whereas the α-glucosidase inhibition type was mixed-type for caffeoyltryptophan and uncompetitive (rarely reported for a-glucosidase inhibitors) for falcarindiol. In addition, molecular docking results showed that these active compounds exhibited good binding affinities toward both PTP1B and α-glucosidase with negative binding energies. The results of the present study demonstrate that these active compounds might be beneficial in the treatment of type 2 diabetes.

New diarylheptanoid dimers as GLP-1 secretagogues and multiple-enzyme inhibitors from Alpinia katsumadai

Ten new diarylheptanoid dimers, katsumadainols C1 − C10 (1–10), were isolated from the seeds of Alpinia katsumada and elucidated by extensive spectroscopic methods, ECD calculations, and single-crystal X-ray diffraction. Their antidiabetic effects were evaluated by the stimulation of GLP-1 secretion in STC-1 cells and inhibition against four diabetes-related enzymes, GPa, α-glucosidase, PTP1B, and DPP4. Compounds 1–5 and 7–10 significantly stimulated GLP-1 secretion by 267.5–433.1% (25.0 μM) and 117.8–348.2% (12.5 μM). Compounds 1–4 exhibited significant inhibition on GPa with IC50 values of 18.0–31.3 μM; compounds 1–5 showed obvious inhibition on α-glucosidase with IC50 values of 6.9–18.2 μM; compounds 1–5 and 10 possessed PTP1B inhibitory activity with IC50 values ranging from 35.5 to 80.1 μM. This investigation first disclosed compounds 1–4 as intriguing GLP-1 secretagogues and GPa, α-glucosidase, and PTP1B inhibitors, which provided valuable clues for searching multiple-target antidiabetic candidates from Zingiberaceae plants.

Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3β,12β,25-triol derivatives as α-glucosidase and PTP1B inhibitors.

The dammarane triterpenoid (20S,24R)-epoxy-dammarane-3β,12β,25-triol obtained from Cyclocarya paliurus in our previous study showed inhibitory activity on α-glucosidase in vitro with an inhibitory ratio of 32.2% at the concentration of 200 μM. In order to reveal the structure-activity relationships (SARs) and get more active compounds, 42 derivatives of (20S,24R)-epoxy-dammarane-3β,12β,25-triol were synthesized by chemical modification on the hydroxyls (C-3 and C-12), rings A and E, and assayed for their α-glucosidase and PTP1B inhibitory activities. Two compounds (8, 26) increased activity against α-glucosidase, and four compounds (8, 15, 26, 42) significantly inhibited PTP1B. It was noted that compounds 8 and 26 could inhibit both α-glucosidase and PTP1B as dual-target inhibitors with IC50 values of 489.8, 467.7 μM (α-glucosidase) and 319.7, 269.1 μM (PTP1B). Compound 26 was revealed to be a mix-type inhibitor on α-glucosidase and a noncompetitive-type inhibitor on PTP1B based on enzyme kinetic study. Furthermore, compound 42 could selectively inhibited PTP1B as a mix-type inhibitor with IC50 value of 134.9 μM, which was 2.5-fold higher than the positive control, suramin sodium (IC50 339.0 μM), but not inhibit α-glucosidase.

Three new cassane-type diterpenoids from Caesalpinia sinensis

Three new cassane-type diterpenoids, namely, (4S)-6β,12α,19-trihydroxy-cass-13(15)-en-16,12-olide (1), cass-13(15)-en-​16,12-olide (2), and 12α-hydroxy-cass-13(15)-en-16,12-olide (3), were isolated from the seeds of Caesalpinia sinensis. The structures of 1–3 were established by extensive spectroscopic analysis, and their absolute configurations were assigned by electronic circular dichroism (ECD) calculations. The inhibitory activities against PTP1B of the isolated compounds were evaluated. The results showed that compound 2 possessed PTP1B inhibitory activity with an IC50 value of 217.45 ± 36.4 μM.

Isothiocyanate From Moringa oleifera Seeds Inhibits the Growth and Migration of Renal Cancer Cells by Regulating the PTP1B-dependent Src/Ras/Raf/ERK Signaling Pathway.

Moringa oleifera Lam. is a tropical and subtropical plant that has been used for centuries as both food and traditional medicine. 4-[(α-L-Rhamnosyloxy) benzyl] isothiocyanate (MIC-1) is an active substance in M. oleifera, with anti-cancer activity. However, whether MIC-1 exerts anti-renal cancer effects is unknown. Therefore, the aim of the present study was to evaluate the effects of MIC-1 on the growth and migration of renal cell carcinoma (RCC) cells and to identify the putative underlying mechanism. We found that, among 30 types of cancer cells, MIC-1 exerted the strongest growth inhibitory effects against 786-O RCC cells. In addition, MIC-1 (10 μM) significantly inhibited the growth of five RCC cell lines, including 786-O, OSRC-2, 769-P, SK-NEP-1, and ACHN cells, but was not toxic to normal renal (HK2) cells. Also, MIC-1 suppressed 786-O and 769-P cell migration and invasion abilities, and reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, MIC-1 induced apoptosis and cell cycle arrest, increased Bax/Bcl-2 ratio, and decreased cell cycle-related protein expression in 786-O cells and 769-P cells. Molecular docking and small-molecule interaction analyses with PTP1B both showed that MIC-1 inhibited PTP1B activity by binding to its active site through hydrogen bonding and hydrophobic interactions. Additionally, MIC-1 could suppress the growth and migration of 786-O cells by inhibiting PTP1B-mediated activation of the Src/Ras/Raf/ERK signaling pathway. In vivo experiments further showed that MIC-1 markedly inhibited the growth of xenograft tumors in mice, and greatly increased Bax/Bcl-2 ratio in tumor tissues. In addition, MIC-1 had no effect on the PTP1B-dependent Src/Ras/Raf/ERK signaling pathway in HCT-116 cells, Hep-G2 cells, and A431 cells. Overall, our data showed that MIC-1 could be a promising, non-toxic, natural dietary supplement for the prevention and treatment of renal cancer.

Atropisomeric 9,10-dihydrophenanthrene/bibenzyl trimers with anti-inflammatory and PTP1B inhibitory activities from Bletilla striata.

Two pairs of novel trimeric dihydrophenanthrene-bibenzyl-dihydrophenanthrene enantiomers (1 and2), the first examples of a dihydrophenanthrene dimer linked to a bibenzyl or dihydrophenanthrene through a C-O-C bond (3 and4), and a pair of rare polymers with a bibenzyl connected to C-8' of the dihydrophenanthro[b]furan moiety via a methylene (5), together with four known compounds (6-9) were isolated from the tubers of Bletilla striata. Their structures including the absolute configurations were determined using spectroscopic data analysis and ECD and NMR calculations, combined with the exciton chirality method or the reversed helicity rule. The atropisomerism of dihydrophenanthrenes and related polymers was considered based on their chiral optical properties, and QM torsion profile calculations, which revealed the racemic mixture form of the polymers. Compounds 4, 5b, 6a and 7b significantly inhibited the production of NO in LPS-induced BV-2 cells, with IC50 values ranging from 0.78 to 5.52 μM. Further mechanistic study revealed that 7b suppressed the expression of iNOS, and suppressed the phosphorylation of the p65 subunit to regulate the NF-κB signaling pathway. Furthermore, compounds 2b, 5a, 5b, 7a and 7b displayed significant protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC50 values of 3.43-12.30 μM.

Root-Extracted Lignanamides from Limonium Gmelinii (Willd.) Kuntze with a Potential PTP1B Inhibitory Activity by Regulating PI3k/AKT Signaling Pathway

Root-Extracted Lignanamides from Limonium Gmelinii (Willd.) Kuntze with a Potential PTP1B Inhibitory Activity by Regulating PI3k/AKT Signaling Pathway

One uncommon bis-sesquiterpenoid from Xisha soft coral Litophyton nigrum

One uncommon sesquiterpenoid dimer (1), a new nardosinane-type sesquiterpenoid (3), along with two known sesquiterpenoids (2 and 4) were isolated from soft coral Litophyton nigrum using a structure-oriented HR-MS/MS approach. The configurations of the isolates were determined by spectroscopic data analyses, including HR-ESI-MS, 1D/2D NMR, single crystal X-ray diffraction, and DP4+ statistical analyses. Compound 3 exhibited potent PTP1B inhibitory activity (IC50 = 10.67 ± 1.81 μg/mL) compared to the positive control.

Dual High-Resolution α-Glucosidase and PTP1B Inhibition Profiling Combined with HPLC-PDA-HRMS-SPE-NMR Analysis for the Identification of Potentially Antidiabetic Chromene Meroterpenoids from Rhododendron capitatum.

Thirteen previously undescribed chromene meroterpenoids, capitachromenic acids A-M (3-6, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b, and 11b), were identified from an ethyl acetate extract of Rhododendron capitatum, using dual high-resolution α-glucosidase and PTP1B inhibition profiling in combination with HPLC-PDA-HRMS-SPE-NMR. In addition, one known chromene meroterpenoid, daurichromenic acid (15), and its biosynthetic precursor, grifolic acid (12), two C-methylated flavanones, (2S)-5,7,4'-trihydroxy-8-methylflavanone (1) and farrerol (2), and two triterpenoids, oleanolic acid (14a) and ursolic acid (14b), were identified. New structures were elucidated by extensive 1D and 2D NMR analysis, and absolute configurations of new chromene meroterpenoids were assigned by analysis of their ECD spectra on the basis of the empirical chromane helicity rule and from Rh2(OCOCF3)4-induced ECD spectra by applying the bulkiness rule. Compounds 5, 9a, 9b, 12, and 15 showed α-glucosidase inhibitory activity with IC50 values ranging from 8.0 to 93.5 μM, while compounds 3, 5, 8b, 9a, 9b, 10b, 11b, 12, and 15 showed PTP1B inhibitory activity with IC50 values ranging from 2.5 to 68.1 μM.

Khayalactone- and phragmalin-type limonoids with PTP1B inhibitory activity from Trichilia sinensis Bentv

An investigation on the extract from the plant Trichilia sinensis Bentv. led to the isolation of 13 new limonoids (1−13), in which two were of khayalactone skeleton and 11 were phragmalin-type limonoids, and eight known phragmalin-type limonoids (14–21). Their structures were elucidated by using spectroscopic techniques and HRESIMS experiment. Compounds 6 and 17 displayed potent protein tyrosine phosphatase 1B inhibitory activity with IC50 values of 1.2 ± 0.1 and 8.1 ± 0.5 μM, respectively.

α-Glucosidase and PTP-1B Inhibitors from Malbranchea dendritica.

An extract from a PDB static culture of Malbranchea dendritica exhibited α-glucosidase and PTP-1B inhibitory activities. Fractionation of the active extract led to the isolation of gymnoascolide A (1), a γ-butenolide, and xanthones sydowinin A (2), sydowinin B (3), and AGI-B4 (4), as well as orcinol (5). Compound 1 exhibited important inhibitory activity against yeast α-glucosidase (IC50 = 0.556 ± 0.009 mM) in comparison to acarbose (IC50 = 0.403 ± 0.010 mM). Kinetic analysis revealed that 1 is a mixed-type inhibitor. Furthermore, compound 1 significantly reduced the postprandial peak in mice during a sucrose tolerance test at the doses of 5.16 and 10 mg/kg. Compound 1 was reduced with Pd/C to yield a mixture of enantiomers 1a and 1b; the mixture showed similar activity against α-glucosidase (IC50 = 0.396 ± 0.003 mM) and kinetic behavior as the parent compound but might possess better drug-likeness properties according to SwissADME and Osiris Property Explorer tools. Docking analysis with yeast α-glucosidase (pdb: 3A4A) and the C-terminal subunit of human maltase-glucoamylase (pdb: 3TOP) predicted that 1, 1a, and 1b bind to an allosteric site of the enzymes. Compounds 1–5 were evaluated against PTP-1B, but only xanthone 3 moderately inhibited in a noncompetitive fashion the enzyme with an IC50 of 0.081 ± 0.004 mM. This result was consistent with that of docking analysis, which revealed that 3 might bind to an allosteric site of the enzyme. From the inactive barley-based semisolid culture of M. dendritica, the natural pigment erythroglaucin (6) and the nucleosides deoxyadenosine (7), adenosine (8), thymidine (9), and uridine (10) were also isolated and identified.

Untargeted Metabolomics Approach for the Discovery of Environment-Related Pyran-2-ones Chemodiversity in a Marine-Sourced Penicillium restrictum.

Very little is known about chemical interactions between fungi and their mollusc host within marine environments. Here, we investigated the metabolome of a Penicillium restrictum MMS417 strain isolated from the blue mussel Mytilus edulis collected on the Loire estuary, France. Following the OSMAC approach with the use of 14 culture media, the effect of salinity and of a mussel-derived medium on the metabolic expression were analysed using HPLC-UV/DAD-HRMS/MS. An untargeted metabolomics study was performed using principal component analysis (PCA), orthogonal projection to latent structure discriminant analysis (O-PLSDA) and molecular networking (MN). It highlighted some compounds belonging to sterols, macrolides and pyran-2-ones, which were specifically induced in marine conditions. In particular, a high chemical diversity of pyran-2-ones was found to be related to the presence of mussel extract in the culture medium. Mass spectrometry (MS)- and UV-guided purification resulted in the isolation of five new natural fungal pyran-2-one derivatives—5,6-dihydro-6S-hydroxymethyl-4-methoxy-2H-pyran-2-one (1), (6S, 1’R, 2’S)-LL-P880β (3), 5,6-dihydro-4-methoxy-6S-(1’S, 2’S-dihydroxy pent-3’(E)-enyl)-2H-pyran-2-one (4), 4-methoxy-6-(1’R, 2’S-dihydroxy pent-3’(E)-enyl)-2H-pyran-2-one (6) and 4-methoxy-2H-pyran-2-one (7)—together with the known (6S, 1’S, 2’S)-LL-P880β (2), (1’R, 2’S)-LL-P880γ (5), 5,6-dihydro-4-methoxy-2H-pyran-2-one (8), (6S, 1’S, 2’R)-LL-P880β (9), (6S, 1’S)-pestalotin (10), 1’R-dehydropestalotin (11) and 6-pentyl-4-methoxy-2H-pyran-2-one (12) from the mussel-derived culture medium extract. The structures of 1-12 were determined by 1D- and 2D-MMR experiments as well as high-resolution tandem MS, ECD and DP4 calculations. Some of these compounds were evaluated for their cytotoxic, antibacterial, antileishmanial and in-silico PTP1B inhibitory activities. These results illustrate the utility in using host-derived media for the discovery of new natural products.

SYNTHESIS AND PTP1B INHIBITORY ACTIVITY OF NOVEL BENZOTHIAZOLE AND 1, 2, 4-TRIAZOLE LINKED ACETAMIDO BENZOIC ACID DERIVATIVES AS ANTIDIABETIC ACTIVITY

The present research reports the synthesis and PTP1B inhibitory activity evaluation of a series of substituted benzthiazole/ 1, 2, 4-triazole linked acetamido benzoic acid derivatives designed based on a lead molecule, 4-methyl-3- (2-(5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-ylthio) acetamido) benzoic acid identified previously in our laboratory. All the synthesized derivatives showed improved PTP1B inhibitory activity, out of which, compound 6c (4- methyl-3-(2-(5-(pyridin-4-yl)-4H-1, 2, 4-triazol-3ylthio) acetamido) benzoic acid) elicited potent PTP1B inhibitory activity with IC50 value 6.45 μM. Furthermore, compound 6c also showed good in vivo antidiabetic activity in streptozotocin-induced diabetes model. Molecular docking studies performed with 6c revealed the binding mechanism of the molecule in the catalytic site of PTP1B. These results demonstrate that compound 6c might serve as a valuable lead molecule for the development of promising antidiabetic agents targeting PTP1B.

Palitantin derivatives from the Antarctic fungus Geomyces sp. 3-1

Two new polyketides, palitantins B and C (1 and 2), along with one known related compound (+)-palitantin (3) were obtained from the culture of the Antarctic fungus Geomyces sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data. Compound 3 showed potent PTP1B inhibitory activity with an IC50 value of 7.9 μM (ursolic acid as positive control, IC50 = 8.3 μM).

Bioactive monoterpene phenol dimers from the fruits of Psoralea corylifolia L.

Nine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1–9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1–9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1–4) were composed of two bakuchiols, one of which was cyclized via a C-7′/ C-12′ single bond to form a six-member ring, and connect to each other by C–4–O–C–13' bonds. Bisbakuchiols (7–9) had a pyran ring by linkage of C–8–O–C–12. In the enzyme assay, compounds 5 and 9 exhibited significant PTP1B inhibitory activities with IC50 values of 0.69 and 0.73 μM, and compounds 1 and 3 showed moderate PTP1B inhibitory activities. Furthermore, a molecular docking simulation of PTP1B and active compounds 5 and 9 showed that these active compounds possess low binding affinities ranging from −6.9 to −7.1 kcal/mol.