2. Academic Validation
  3. Potential Therapeutic Target Protein Tyrosine Phosphatase-1B for Modulation of Insulin Resistance with Polyphenols and Its Quantitative Structure-Activity Relationship

Potential Therapeutic Target Protein Tyrosine Phosphatase-1B for Modulation of Insulin Resistance with Polyphenols and Its Quantitative Structure-Activity Relationship

  • Molecules. 2022 Mar 29;27(7):2212. doi: 10.3390/molecules27072212.
Prangya Rath 1,  Anuj Ranjan 2,  Arabinda Ghosh 3,  Abhishek Chauhan 4,  Manisha Gurnani 1,  Hardeep Singh Tuli 5,  Hamza Habeeballah 6,  Mustfa F Alkhanani 7,  Shafiul Haque 8 9,  Kuldeep Dhama 10,  Naval Kumar Verma 11,  Tanu Jindal 4
Affiliations

Affiliations

  • 1 Amity Institute of Environmental Sciences, Amity University, Noida 201303, India.
  • 2 Academy of Biology and Biotechnology, Southern Federal University, 344006 Rostov-on-Don, Russia.
  • 3 Microbiology Division, Department of Botany, Gauhati University, Guwahati 781014, India.
  • 4 Amity Institute of Environmental Toxicology Safety and Management, Amity University, Noida 201303, India.
  • 5 Department of Biotechnology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India.
  • 6 Faculty of Applied Medical Sciences, King Abdulaziz University, Rabigh Branch, Rabigh 25732, Saudi Arabia.
  • 7 Emergency Service Department, College of Applied Sciences, AlMaarefa University, Riyadh 11597, Saudi Arabia.
  • 8 Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan 45142, Saudi Arabia.
  • 9 Faculty of Medicine, Bursa Uludağ University Görükle Campus, Nilüfer 16059, Turkey.
  • 10 Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, India.
  • 11 Homeopathy, Ministry of Ayush, Ayush Bhawan, B Block, GPO Complex INA, New Delhi 110023, India.
PMID: 35408611 DOI: 10.3390/molecules27072212
Abstract

The increase in the number of cases of type 2 diabetes mellitus (T2DM) and the complications associated with the side effects of chemical/synthetic drugs have raised concerns about the safety of the drugs. Hence, there is an urgent need to explore and identify natural bioactive compounds as alternative drugs. Protein tyrosine Phosphatase 1B (PTP1B) functions as a negative regulator and is therefore considered as one of the key protein targets modulating Insulin signaling and Insulin resistance. This article deals with the screening of a database of Polyphenols against PTP1B activity for the identification of a potential inhibitor. The research plan had two clear objectives. Under first objective, we conducted a quantitative structure-activity relationship analysis of Flavonoids with PTP1B that revealed the strongest correlation (R2 = 93.25%) between the number of aromatic bonds (naro) and inhibitory concentrations (IC50) of PTP1B. The second objective emphasized the binding potential of the selected Polyphenols against the activity of PTP1B using molecular docking, molecular dynamic (MD) simulation and free energy estimation. Among all the Polyphenols, silydianin, a flavonolignan, was identified as a lead compound that possesses drug-likeness properties, has a higher negative binding energy of -7.235 kcal/mol and a PKD value of 5.2. The free energy-based binding affinity (ΔG) was estimated to be -7.02 kcal/mol. MD simulation revealed the stability of interacting residues (Gly183, Arg221, Thr263 and Asp265). The results demonstrated that the identified polyphenol, silydianin, could act as a promising natural PTP1B inhibitor that can modulate the Insulin resistance.

Keywords

QSAR; catalytic active site; diabetes; docking; insulin resistance; molecular dynamic simulation; polyphenols.

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