Multi-Targeted Molecular Docking, Pharmacokinetics, and Drug-Likeness Evaluation of Okra-Derived Ligand Abscisic Acid Targeting Signaling Proteins Involved in the Development of Diabetes

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. Keeping 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 reductase, glucokinase, glutamine-fructose-6-phosphate amidotransferase (GFAT), peroxisome proliferator-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 potential. 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 hazardous effect following all current drug-likeness guidelines such as Lipinski, Ghose, Veber, Egan, and Muegge.

Repurposing Mitragynine as Anti-SARS-CoV-2 Agent Evidenced by In Silico Predictive Approach

“…In terms of bioavailability, drug-likeness indicates the possibility of a molecule becoming an oral drug. The bioavailability score indicates whether a molecule will have at least 10% oral bioavailability in rats [44]. With a bioavailability score of 0.85, we conclude that mitragynine does not contradict the Lipinski, Ghose, Veber, Egan, and Muegge drug-likeness standards.…”

Electrochemical, Ultrasensitive, and Selective Detection of Nitrite and H2O2: Novel Macrostructured Phthalocyanine with Composite MWCNTs on a Modified GCE

“…Usually, AutoDock Vina gives nine confirmations. In general, the lower the binding energy, the greater the ligands’ and complexes’ binding affinity to the protein molecule . Therefore, a lower binding affinity value was considered for further studies.…”

“…In general, the lower the binding energy, the greater the ligands' and complexes' binding affinity to the protein molecule. 74 Therefore, a lower binding affinity value was considered for further studies. The results of AutoDock Vina were analyzed using BIOVIA discovery studio and Pymol visualization tools.…”

Synthesis and Anti-microbial activity of Isoxazole derivates via Nitrile Oxide, 1,3-Dipolar Cycloaddition Reaction

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