Investigating the Interactions of Human Organic Cation Transporter 1 and Enteropeptidase with Metformin and Its Derivative to Alleviate Side Effects in Diabetes Treatments
Year: 2025
Type: article
Abstract: Diabetes is a chronic disease that is characterized by elevated blood sugar levels. Once diagnosed, patients will live with various types of treatments for the rest of their lives. The disease can burden families and result in damage to other organ systems or death. The most common treatment for type 2 diabetes is an oral medicine called metformin, coupled with life style changes and other therapies. The drug acts by binding to the protein called human organic cation transporter 1 (hOCT1). Although the medicine is low-cost, effective, and was recognized several health organizations, it still leads to side effects. The interaction of the drug with enteropeptidase is known to cause impaired digestion, which results in diarrhea, nausea, and other gastrointestinal side effects. In attempt to enhance the therapeutic effectiveness of the drug while reducing the side effects, a new derivative of metformin that has greater binding affinityto hOCT1 and lower binding affinity to enteropeptidase. Key interactions and residues were identified, and by adding an aromatic ring with substituent of hydroxyl and amine groups to the drug, H bonding and Pi-Pi interactions with hOCT1 were enhanced, increasing the binding efficacy. On the other hand, addition of bulkier substituent disrupted the H bond between the drug and a key residue HIS 57.B, allowing for the binding to be less effective in turns to minimize the side effects.
Source: Theoretical and Natural Science
Author: Phoebe Tszki Zhang
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: hybrid
OpenAlex ID: W4413962076