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Chinese Journal of Organic Chemistry >

0 202604010 - 202604010

DOI: https://doi.org/10.6023/cjoc202604010

ARTICLE

Betulinic Acid-triazole Hybrids as Novel PTP1B Inhibitors: Synthesis and Bioactivity Evaluation

  • Yufei Zhang ,
  • Lirong Tan ,
  • Yueyuan Zhong ,
  • Tongzheng Liu ,
  • Shao-Hua Wang
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  • aCollege of Pharmacy, Jinan University, Guangzhou, GuangdongCity 511436;
    bSchool of Pharmacy, Lanzhou University, Lanzhou, Gansu 730000
†These authors contributed equally to this work.

Received date: 2026-04-07

  Revised date: 2026-05-13

  Online published: 2026-05-27

Supported by

National Key R&D Program of China (2023YFA1506404), the Science and Technology Program of Gansu Province (23ZDFA003, 23JRRA1028,23ZDFA015, 24ZD13FA017), the Lanzhou Science and Technology Planning Project (2023-QN-18, 2023-1-17, 2024-1-17) (No. )

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Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and leptin signaling pathways and has emerged as a promising therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). Inhibition of PTP1B enhances insulin sensitivity and offers a potential strategy for managing both diabetes and obesity. In this study, 35 betulinic acid (BA)-triazole hybrids (BAT1-BAT35) were synthesized and evaluated for their PTP1B inhibitory activities. All synthesized BA hybrids exhibited significantly higher PTP1B inhibitory activity than parent compound BA. Notably, BAT28 demonstrated the most potent activity, with an IC50 value of 1.06 ± 0.06 μM. Kinetic analysis revealed that BAT28 acted as a mixed-type PTP1B inhibitor. CD spectra indicated that BAT28 bound to PTP1B and induced conformation changes in the enzyme. Molecular docking studies further confirmed that BAT28 interacted with the active site of PTP1B. In vivo experiments using an oral glucose tolerance test (OGTT) showed that BAT28 effectively reduced postprandial blood glucose levels in mice. Additionally, BAT28 exhibited favorable drug-like properties based on in silico predictions. These findings suggested that BAT28 represented a promising lead compound for the development of novel PTP1B inhibitors.

Key words： Betulinic acid; Triazole; PBP1B inhibitor

Cite this article

Yufei Zhang , Lirong Tan , Yueyuan Zhong , Tongzheng Liu , Shao-Hua Wang . Betulinic Acid-triazole Hybrids as Novel PTP1B Inhibitors: Synthesis and Bioactivity Evaluation[J]. Chinese Journal of Organic Chemistry, 0 : 202604010 -202604010 . DOI: 10.6023/cjoc202604010

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