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<p>Diabetes mellitus (DM) remains a global health challenge, necessitating the exploration of novel therapeutic strategies. Dipeptidyl Peptidase-4 (DPP-4) inhibitors have emerged as effective treatments by enhancing incretin-mediated insulin secretion. Here, we investigated bioactive compounds from three African plants—<i>Ocimum gratissimum</i>, <i>Colocasia esculenta L.</i>, and <i>Jatropha curcas L.</i>—as potential DPP-4 inhibitors through an integrative computational approach. Using molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling, molecular dynamics (MD) simulations, and MM-GBSA (molecular mechanics energies combined with generalized Born and surface area continuum solvation) free energy calculations, we assessed the drug-likeness, pharmacokinetic properties, and stability of these compounds. Also, 100-ns MD simulation with MM-GBSA analysis using Desmond and Prime modules, respectively, was carried out on the top two hit compounds. The results here revealed that salvigenin and daidzein have good drug-likeness profiles, binding potentials, acceptable ADMET properties, and more stable protein–ligand complexes. Conclusively, the current computer-aided modeling showed that daidzein and salvigenin might have the potential to inhibit DPP-4 activity in diabetes mellitus. Due to this finding, we suggest robust wet laboratory experiments to facilitate the deployment of both compounds in the fight to manage diabetes mellitus.</p> Graphical abstract <p></p>

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In-silico discovery of Dipeptidyl Peptidase-4 inhibitors from African medicinal plants: Molecular docking, ADMET, dynamics simulation, and MM-GBSA analyses

  • 期刊论文

  • 发表日期：

    2025年1月31日

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  • Ishola Abeeb Akinwumi,
  • Amgad M. Rabie,
  • Kalpana Katiyar,
  • Adeola Ajayi,
  • Ridwan Opeyemi Bello,
  • Abdullahi Tunde Aborode,
  • Abu Tayab Moin,
  • Jannatul Ferdoush,
  • Adedeji Ogunyemi,
  • Precious Etinosa,
  • Abraham Osinuga,
  • Babatunde Samuel Obadawo,
  • Victoria Gbonjubola Awolola,
  • Aeshah Ali Ahmad Awaji,
  • Haruna Isiyaku Umar,
  • Ridwan Olamilekan Adesola,
  • Waheed Sakariyau Adio,
  • Bisi Olajumoke Adeoye,
  • Oluwatosin M. Adeyemo,
  • Anne Adebukola Adeyanju,
  • Akinola Olusegun Oyewole,
  • Jane Aruorivwooghene Ibude,
  • Oluwatope Richard Ojo,
  • Abdullahi Jamiu,
  • Isreal Ayobami Onifade

摘要

Diabetes mellitus (DM) remains a global health challenge, necessitating the exploration of novel therapeutic strategies. Dipeptidyl Peptidase-4 (DPP-4) inhibitors have emerged as effective treatments by enhancing incretin-mediated insulin secretion. Here, we investigated bioactive compounds from three African plants—Ocimum gratissimum, Colocasia esculenta L., and Jatropha curcas L.—as potential DPP-4 inhibitors through an integrative computational approach. Using molecular docking, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling, molecular dynamics (MD) simulations, and MM-GBSA (molecular mechanics energies combined with generalized Born and surface area continuum solvation) free energy calculations, we assessed the drug-likeness, pharmacokinetic properties, and stability of these compounds. Also, 100-ns MD simulation with MM-GBSA analysis using Desmond and Prime modules, respectively, was carried out on the top two hit compounds. The results here revealed that salvigenin and daidzein have good drug-likeness profiles, binding potentials, acceptable ADMET properties, and more stable protein–ligand complexes. Conclusively, the current computer-aided modeling showed that daidzein and salvigenin might have the potential to inhibit DPP-4 activity in diabetes mellitus. Due to this finding, we suggest robust wet laboratory experiments to facilitate the deployment of both compounds in the fight to manage diabetes mellitus.

Graphical abstract