Dimeric phenalenones from Talaromyces sp. (IQ-313) inhibit hPTP1B1-400: Insights into mechanistic kinetics from in vitro and in silico studies

Jiménez-Arreola, Brenda S.; Aguilar-Ramírez, Enrique; Cano‐Sánchez, Patricia; Morales-Jiménez, Jesús; González-Andrade, Martín; Medina-Franco, José L.; Rivera‐Chávez, José

doi:10.1016/j.bioorg.2020.103893

Cited by 21 publications

(16 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bioassay results for this set of compounds indicated that only compounds 3 and 7 inhibited h PTP1B 1–400 . Interestingly, compound 3 only inhibits this enzyme by 50% at concentrations ranging from 380 μM to 1 mM, whereas the IC 50 value calculated for 7 was 33.1 μM, in agreement with previously reported data . Compound 7 inhibited the hydrolase activity of yeast α-glucosidase with an IC 50 of 7.5 μM, similar to that described in the literature .…”

Section: Results and Discussionmentioning

confidence: 99%

“…Interestingly, compound 3 only inhibits this enzyme by 50% at concentrations ranging from 380 μM to 1 mM, whereas the IC 50 value calculated for 7 was 33.1 μM, in agreement with previously reported data. 32 Compound 7 inhibited the hydrolase activity of yeast α-glucosidase with an IC 50 of 7.5 μM, similar to that described in the literature. 33 Hydroxy-neo-clerodanes have previously been reported as α-glucosidase inhibitors with IC 50 values ranging from 113 μM to higher than 5 mM.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The plasmid was transformed in Escherichia coli Rosetta (DE3) pLysS strain using LB medium. Protein expression was induced using 1 mM IPTG at 20 °C for 16 h. Purification of h PTP1B 1–400 was carried out following the procedure described by Krishnan et al and Jiménez-Arreola et al, with some modifications. ,, Briefly, cells were resuspended in lysis buffer (50 mM HEPES pH 7.2, 150 mM NaCl, 10 mM imidazole, and 2 mM TCEP) and lysed using sonication in an ice bath (4 °C). Lysates were then centrifuged and purified using affinity chromatography by gravity (1 mL/min) with 50 mM HEPES pH 7.4, 100 mM NaCl, 300 mM imidazole, and 1.5 mM DTT.…”

Section: Methodsmentioning

confidence: 99%

“…Buffer solution was exchanged using 50 mM HEPES pH 7.4, 100 mM NaCl, and 1.5 mM DTT. The protein was used immediately or stored at −20 °C in 50 mM HEPES pH 7.4, 100 mM NaCl, 2 mM DTT, and 4% glycerol. ,, …”

Section: Methodsmentioning

confidence: 99%

“…Buffer solution was exchanged using 50 mM HEPES pH 7.4, 100 mM NaCl, and 1.5 mM DTT. The protein was 21,22,32 hPTP1B 1−400 Inhibition Assay. The extract (500 ppm), fractions (500 ppm), and isolated compounds, including ursolic acid (7, positive control, 600 μM), were dissolved in DMSO.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

See 4 more Smart Citations

Hydroxy-neo-Clerodanes and 5,10-seco-neo-Clerodanes from Salvia decora

et al. 2020

Self Cite

View full text Add to dashboard Cite

Preliminary analysis of the mass spectrometric (MS) and NMR spectroscopic data of the primary fractions from the biologically active extract of Salvia decora revealed spectra that are characteristic for neo-clerodane-type diterpenoids. MSguided isolation of the bioactive fractions led to the isolation of three new chemical entities, including two hydroxy-neo-clerodanes (1 and 2) and one acylated 5,10-seco-neo-clerodane (3), along with three known diterpenoids (4−6), ursolic acid (7), and eupatorin (8). The structures of the new compounds were established by analysis of the 1D and 2D NMR and MS data, whereas their absolute configuration was deduced using a combination of experimental and theoretical ECD data and confirmed by X-ray crystallography (1 and 4). Furthermore, compounds 1, 3, 4, and 6−8 were evaluated as hPTP1B 1−400 (human protein tyrosine phosphatase) inhibitors, where 7 showed the best activity, with an IC 50 value in the lower μM range. Additionally, compound 7 was evaluated as an α-glucosidase inhibitor. The affinity constant of the 7-hPTP1B 1−400 complex was determined by quenching fluorescence experiments (k a = 1.3 × 10 4 M −1 ), while the stoichiometry ratio (1:1 protein−ligand) was determined by a continuous variation method.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

See 3 more Smart Citations

Hydroxy-neo-Clerodanes and 5,10-seco-neo-Clerodanes from Salvia decora

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Virtual and in Vitro Screening Employing a Repurposing Approach Reveal 13‐cis‐Retinoic Acid is a PTP1B Inhibitor

Del Carmen Navarrete‐Mondragón,

Cortés‐Benítez,

Elena Mendieta‐Wejebe

et al. 2024

ChemMedChem

View full text Add to dashboard Cite

Current treatments for type 2 diabetes (T2D) mainly rely on exercise, dietary control, and anti‐diabetic drugs to enhance insulin secretion and improve insulin sensitivity. However, there is a need for more therapeutic options. A potential target that has attracted attention is the protein tyrosine phosphatase 1B (PTP1B), which negatively regulates the insulin signaling pathway. In this work, a comprehensive computational screening was carried out using cheminformatics and molecular docking on PTP1B, employing a rigorous repurposing approach. The screening involved approved drugs and compounds under research as anti‐diabetics that bind to targets such as peroxisome proliferator‐activated receptor gamma (PPAR‐gamma) and alpha‐glucosidase. Some computational hits were then meticulously tested in vitro against PTP1B; particularly the 13‐cis‐retinoic acid ( 3a) showed an IC 50 of 0.044 mM and competitive inhibition. Molecular dynamics studies agrees that 3a can bind to the catalytic binding site of PTP1B. It is worth mentioning that 3a has been reported by the first time as an inhibitor of PTP1B in this work, making it a potentially valuable candidate for further studies in D2T treatment.

show abstract

Ants/Nest-Associated Fungi and Their Specialized Metabolites: Taxonomy, Chemistry, and Bioactivity

Aguilar-Colorado

Rivera‐Chávez

2023

Rev. Bras. Farmacogn.

View full text Add to dashboard Cite

Microscopic fungi occupy a vast number of habitats, are taxonomically diverse, degrade complex substrates, and have stood out for their capacity to biosynthesize a plethora of specialized metabolites. Such molecules are structurally diverse, and many have applications in fundamental and applied sciences, for example, in medicine, material sciences, food chemistry, textile and pharmaceutical industries, and agronomy, among other fields. However, despite the tremendous biotechnological value of fungi, these organisms are understudied, limiting the knowledge to their taxonomy, chemistry, and some putative applications. Notably, some specific habitats remain unexplored in terms of their mycobiota. Based on these considerations, this review describes the known fungal diversity associated with ants/nests, their metabolic potential, and the possible applications of their specialized metabolites in drug discovery programs focused on developing treatments for human diseases. According to this revision, fungal diversity has been studied by applying conventional methodologies such as isolation and morphological identification of soil fungi from mounds and nest chambers, and indirectly from ants’ cuticles and glands. The subfamilies, genera, taxonomical information, and geographical origin of ants from which filamentous fungi and yeast are commonly isolated are also described. Furthermore, some important information is presented concerning the difference between the ant-associated mycobiota and that in the surroundings, discarding the extrapolation of the chemical and biological information known for soil fungi. Altogether, this review evidenced the lack of information regarding the chemical composition of ant-associated fungi, encouraging research focused on exploring the chemistry biosynthesized from ants’ mycobiota, as well as the elucidation of their allelopathic potential inside the nests. Graphical Abstract

show abstract

Dimeric phenalenones from Talaromyces sp. (IQ-313) inhibit hPTP1B1-400: Insights into mechanistic kinetics from in vitro and in silico studies

Cited by 21 publications

References 46 publications

Hydroxy-neo-Clerodanes and 5,10-seco-neo-Clerodanes from Salvia decora

Hydroxy-neo-Clerodanes and 5,10-seco-neo-Clerodanes from Salvia decora

Virtual and in Vitro Screening Employing a Repurposing Approach Reveal 13‐cis‐Retinoic Acid is a PTP1B Inhibitor

Ants/Nest-Associated Fungi and Their Specialized Metabolites: Taxonomy, Chemistry, and Bioactivity

Contact Info

Product

Resources

About