Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: Perspectives for Developing of Novel Insulin-Mimetic Drugs
Abstract
:1. Introduction
2. Results
2.1. Oxidative Cleavage of Phosphoeleganin Affords Compounds 2 and 3
2.2. Synthetic Approach for Obtaining Compounds 4a–9b
2.3. Preliminary Screening on AR and PTP1B Enzymes of Compounds 2–4b and 7a–9b
2.4. Definition of 3 and 8a Mechanism of Action on PTP1B
2.5. Evaluation of 3 and 8a Interaction with PTP1B by In Silico Docking Analyses
2.6. Analysis of Insulin Signalling Pathway in C2C12 Cells Treated with Compound 3
2.7. Glucose Uptake Assay of Compound 3
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Synthesis of Compounds 2 and 3
4.3. Synthesis of the Series of Phosphoeleganin-Based Simplified Analogues 4a–9b
4.4. Enzymatic Assay
4.4.1. Enzymatic Assays with PTP1B
4.4.2. AR Enzymatic Assay
4.5. Determination of the IC50 Values and Reversibility Assay with PTP1B
4.6. Determination of the Mechanism of Inhibition on PTP1B
4.7. Cell Cultures
4.8. Insulin Signalling Pathway Analysis
4.9. Glucose Uptake Assay
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compounds | IC50 (µM) |
---|---|
Phosphoeleganin | 0.7 ± 0.1 |
3 | 6.7 ± 3.3 |
8a | 16.0 ± 2.0 |
9a | 83.0 ± 15.0 |
8b | 37.1 ± 6.5 |
9b | 63.0 ± 14.0 |
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Casertano, M.; Genovese, M.; Piazza, L.; Balestri, F.; Del Corso, A.; Vito, A.; Paoli, P.; Santi, A.; Imperatore, C.; Menna, M. Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: Perspectives for Developing of Novel Insulin-Mimetic Drugs. Pharmaceuticals 2022, 15, 325. https://doi.org/10.3390/ph15030325
Casertano M, Genovese M, Piazza L, Balestri F, Del Corso A, Vito A, Paoli P, Santi A, Imperatore C, Menna M. Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: Perspectives for Developing of Novel Insulin-Mimetic Drugs. Pharmaceuticals. 2022; 15(3):325. https://doi.org/10.3390/ph15030325
Chicago/Turabian StyleCasertano, Marcello, Massimo Genovese, Lucia Piazza, Francesco Balestri, Antonella Del Corso, Alessio Vito, Paolo Paoli, Alice Santi, Concetta Imperatore, and Marialuisa Menna. 2022. "Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: Perspectives for Developing of Novel Insulin-Mimetic Drugs" Pharmaceuticals 15, no. 3: 325. https://doi.org/10.3390/ph15030325
APA StyleCasertano, M., Genovese, M., Piazza, L., Balestri, F., Del Corso, A., Vito, A., Paoli, P., Santi, A., Imperatore, C., & Menna, M. (2022). Identifying Human PTP1B Enzyme Inhibitors from Marine Natural Products: Perspectives for Developing of Novel Insulin-Mimetic Drugs. Pharmaceuticals, 15(3), 325. https://doi.org/10.3390/ph15030325