Structural and molecular insights of protein tyrosine phosphatase 1B (PTP1B) and its inhibitors as anti-diabetic agents

Paul, Abhik; Sarkar, Arnab; Banerjee, Tanmoy; Maji, Avik; Sarkar, Shrabanti; Paul, Sourav; Karmakar, Sanmoy; Ghosh, Nilanjan; Maity, Tapan K.

doi:10.1016/j.molstruc.2023.136258

Cited by 8 publications

(1 citation statement)

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“…Natural products and synthesized compounds are potential sources in the search for new PTP1B inhibitors . Monoterpene and sesquiterpene-derived meroterpenoids have been recently reported to modulate PTP1B inhibitory activities. , Preliminary screening of isolated compounds 1 - 13 against the PTP1B enzyme at a concentration of 10 μM revealed that compounds 4 , 9 , and 13 exhibited potential PTP1B inhibitory activities (Table ).…”

Section: Resultsmentioning

confidence: 99%

Chalcone-Monoterpene Derivatives from the Buds of Cleistocalyx operculatus and Their Potential as Protein Tyrosine Phosphatase 1B Inhibitors

Mai,

Ponce-Zea,

Doan

et al. 2024

J. Nat. Prod.

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Four new compounds, racemic chalcone-monoterpene hybrids (1−3) and a chalcone (9), along with nine known compounds (4−8, 10−13), have been isolated from the buds of Cleistocalyx operculatus. The chemical structures of the isolated compounds were identified through NMR data analysis and confirmed by computational methods, including electronic circular dichroism (ECD) calculations, and further synthetic approaches. Compounds 1−5 were synthesized via a Diels−Alder reaction, a process informed by biomimetic condensation studies that combined chalcones and monoterpenes. These synthetic approaches also yielded various unnatural chalcone-monoterpene derivatives (14−23). The inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) of both naturally isolated and synthetically obtained compounds were evaluated. Compounds 4, 9, 13, and 16b exhibited potent PTP1B inhibitory activity, with IC 50 values ranging from 0.9 ± 0.2 to 3.9 ± 0.7 μM. The enantiomers (+)-4 and (−)-16b showed enhanced activity compared to their respective enantiomers. Kinetic studies indicate that all active compounds inhibit PTP1B through mixed mechanisms, and molecular docking simulations agree with the experimental assays on PTP1B. Our results suggest that chalcone-meroterpene adducts from the buds of C. operculatus exhibit potential as antidiabetic agents, partly due to their PTP1B enzyme inhibition.

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Section: Resultsmentioning

confidence: 99%