Multi-targeted molecular docking, pharmacokinetics, and drug-likeness evaluation of okra-derived ligand abscisic acid targeting signaling proteins involved in the development of diabetes

Syed Amir Ashraf, Abd Elmoneim O. Elkhalifa, Khalid Mehmood, Mohd Adnan, Mushtaq Ahmad Khan, Nagat Elzein Eltoum, Anuja Krishnan, Mirza Sarwar Baig

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Diabetes mellitus is a global threat affecting millions of people of different age groups. In recent years, the development of naturally derived anti-diabetic agents has gained popularity. Okra is a common vegetable containing important bioactive components such as abscisic acid (ABA). ABA, a phytohormone, has been shown to elicit potent anti-diabetic effects in mouse models. Keep-ing its anti-diabetic potential in mind, in silico study was performed to explore its role in inhibiting proteins relevant to diabetes mellitus-11β-hydroxysteroid dehydrogenase (11β-HSD1), aldose re-ductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome pro-liferator-activated receptor-gamma (PPAR-gamma), and Sirtuin family of NAD(+)-dependent protein deacetylases 6 (SIRT6). A comparative study of the ABA-protein docked complex with already known inhibitors of these proteins relevant to diabetes was compared to explore the inhibitory po-tential. Calculation of molecular binding energy (ΔG), inhibition constant (pKi), and prediction of pharmacokinetics and pharmacodynamics properties were performed. The molecular docking investigation of ABA with 11-HSD1, GFAT, PPAR-gamma, and SIRT6 revealed considerably low binding energy (ΔG from −8.1 to −7.3 Kcal/mol) and predicted inhibition constant (pKi from 6.01 to 5.21 µM). The ADMET study revealed that ABA is a promising drug candidate without any haz-ardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.

Original languageEnglish
Article number5957
JournalMolecules
Volume26
Issue number19
DOIs
Publication statusPublished - Oct 1 2021

Keywords

  • Abscisic acid
  • Anti-diabetic
  • Diabetes mellitus
  • Molecular docking
  • Nutraceuticals
  • Okra
  • Phytohormones

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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