Protein tyrosine phosphatase 1B inhibitors from the fungus Malbranchea albolutea

Díaz-Rojas, Miriam; Raja, Huzefa A.; González-Andrade, Martín; Rivera‐Chávez, José; Rangel‐Grimaldo, Manuel; Rivero‐Cruz, Isabel; Mata, Rachel

doi:10.1016/j.phytochem.2021.112664

Cited by 16 publications

(19 citation statements)

References 55 publications

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“…To test the inhibitory activity of the compounds against PTP1B, a spectrocolorimetric method previously described was employed [ 59 , 60 ]. The compounds and positive control were dissolved in DMSO or buffer solution [50 mM; Tris-HCI Buffer, pH 6.8], DL-dithiothreitol 1.5 mM, all from Sigma–Aldrich, St. Louis, MO, USA.…”

Section: Methodsmentioning

confidence: 99%

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

et al. 2021

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Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 µM) than that of positive controls ursolic acid (IC50 = 5.6 µM), claramine (IC50 = 13.7 µM) and suramin (IC50 = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.

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Section: Methodsmentioning

confidence: 99%

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

et al. 2021

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“…From the inactive barley-based solid culture of M. dendritica, the natural pigment erythroglaucin (6) 20 and the nucleosides deoxyadenosine (7), adenosine (8), thymidine (9), and uridine (10) were isolated and identified by comparison of their NMR data (Figures S12−S19 and Tables S6−S9) with those in the literature; 31 in addition, thymidine (9) was identified by X-ray diffraction analysis (Figure S20). All isolated compounds are shown in Figure 1.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…52 To place the strain ATCC 34527 in a phylogenetic framework, we downloaded all types and other sequences from various closely related Malbranchea and Auxarthron spp 53−55 and performed a Maximum Likelihood analysis using methods detailed recently. 8 ModelFinder 56 predicted TIM3e+I+G4 as the best fitting substitution model according to the Akaike Information Criterion. 57 The trimmed nucleotide alignment after removing ambiguous nucleotide positions with GBlocks 58,59 was then used to run the Maximum Likelihood analysis using IQ-Tree implemented using the program PhyloSuite with 5000 Ultrafast bootstrapping.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…A recombinant human protein tyrosine phosphatase 1B (PTP-1B) was used. 8 The fungal extract, isolated compounds, and positive control (ursolic acid) were dissolved in DMSO or tris buffer solution (100 mM pH = 6.8). Aliquots of 0−10 μL of testing materials (triplicated) were incubated for 5 min with 20 μL of 1.56 mg/mL PTP-1B enzyme solution.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…7 Finally, Malbranchea albolutea Sigler & Carmichael biosynthesizes ardeemin derivatives with potent PTP-1B inhibitory effects. 8 Malbranchea dendritica Sigler & Carmichael is a fungus isolated from soil worldwide. 9 From the chemical and pharmacological point of view, this species has not been investigated.…”

Section: ■ Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Antidiabetic Potential of a Trimeric Anthranilic Acid Peptide Isolated from Malbranchea flocciformis

Rebollar‐Ramos,

Ovalle‐Magallanes,

Raja

et al. 2024

Chemistry & Biodiversity

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Compound 3, a trimeric anthranilic acid peptide, and another three metabolites were isolated from an organic extract from the culture medium of Malbranchea flocciformis ATCC 34530. The chemical structure proposed previously for 3 was unequivocally assigned via synthesis and X‐ray diffraction analysis. Tripeptide 3 showed insulinotropic properties by decreasing the postprandial peak in healthy and hyperglycemic mice. It also increased glucose‐induced insulin secretion in INS‐1E at 5µM, specifically at higher glucose concentrations. These results revealed that 3 might act as an insulin sensitizer and a non‐classical insulin secretagogue. Altogether, these findings are in harmony with the in vivo oral glucose tolerance test and acute oral hypoglycemic assay. Finally, the chemical composition of the extract was established by the Global Natural Products Social Molecular Network platform. Phylogenetic analysis using the internal transcribed spacer region revealed that M. flocciformis ATCC 34530 is related to the Malbrancheaceae.

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Protein tyrosine phosphatase 1B inhibitors from the fungus Malbranchea albolutea

Cited by 16 publications

References 55 publications

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

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

Antidiabetic Potential of a Trimeric Anthranilic Acid Peptide Isolated from Malbranchea flocciformis

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