An In Silico approach to identify solubilising agents for improving the antidiabetic activity of verbenone
DOI:
https://doi.org/10.53704/Keywords:
Verbenone, antidiabetic, ADME parameters, in silico approach, solubilityAbstract
Natural products are used globally to manage diseases, including diabetes mellitus. Verbenone, a component of Daucus carota seed, has been shown to exhibit antidiabetic activity; however, its low solubility due to its nonpolar nature limits its use. Enhancing verbenone's solubility will significantly improve its bioactivity as an antidiabetic agent. This study aims to employ an in silico approach to identify a soluble agent that enhances the antidiabetic activity of verbenone. The structures of verbenone, acarbose, and the identified chemical compounds (L-arginine, gelucire, lysine, eudragit, ethylene glycol, and poloxamer), all with the potential to increase solubility by more than 10-fold, were downloaded in SDF format from the PubChem database. The binding energies were computed using Autodock vina screening software with human salivary α-amylase, α-glucosidase, and pyruvate dehydrogenase kinase. At the same time, physicochemical properties and ADME parameters were predicted using the SwissADME server. The binding energies for L-arginine and gelucire ranged from -4.6 to -6.1 Kcal/mol compared with acarbose (-6.5 to -7.4 Kcal/mol) and verbenone (-5.7 to -6.1 Kcal/mol), respectively. Ethylene glycol and poloxamer have higher binding energies of -2.3 to -3.2 Kcal/mol, respectively. The ligands interacted with different amino acid residues. L-arginine, gelucire, and ethylene glycol are very soluble and do not violate Lipinski’s rule of 5, with high gastrointestinal absorption except for L-arginine. Moreover, the compounds do not cross the blood-brain barrier. L-arginine, gelucire, lysine, and eudragit may be suitable polymers to enhance the antidiabetic activity of verbenone when used as solubilisers in diabetes treatments.
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Copyright (c) 2025 Fatima Mahmoud Aliyu, Ahmad Mallam Ado, Uzaifa Mustapha Adam, Oluremi Saliu, Ayodeji Oluwafemi IDOWU, Habibu Tijjani
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