Title

Molecular docking analysis of PPARγ with phytochemicals from Moroccan medicinal plants

Authors

Lamiae Elkhattabi^¹,²,*, Salwa Zouhdi¹, Fairouz Moussetad¹, Anass Kettani¹,Abdelhamid Barakat² & Rachid Saile¹  

Affiliation

¹Laboratory of Biology and Health, Faculty of Sciences Ben M’Sik, Hassan II University of    Casablanca,   Morocco; Laboratory of Genomics and Human Genetics, Institut Pasteur du Maroc, Casablanca; *Corresponding author

Email

Lamiae Elkhattabi – E-mail: lamiaeelkhattabi@gmail.com

Salwa Zouhdi - E-mail: salwa.zouhdi-etu@etu.univh2c.ma

Fairouz Moussetad – E-mail: fairouz.moussetad-etu@etu.univh2c.ma

Abdelhamid Barakat - E-mail: barakat.abdelhamid@yahoo.fr

Rachid Saile - E-mail: rachid.saile@univh2c.ma; Fax: +212520420959 

Article Type

Research Article

Date

Received July 1, 2023; Revised July 31, 2023; Accepted July 31, 2023, Published July 31, 2023

PPARγ agonists play a crucial role in regulating metabolic homeostasis for treating type-2 diabetes (T2D). Due to the adverse side effects associated with thiazolidinediones, a class of PPARγ agonists, there is a growing interest in identifying natural compounds from medicinal plants that have the potential to bind PPARγ. In this study, we extensively investigated Moroccan phytochemicals using computational structure-based screening with the crystal structure of the PPARγ ligand-binding domain (PDB ID: 7awc) to discover novel phytochemicals targeting PPARγ. The docking results of 540 Moroccan phytochemicals were integrated into online databases for further exploitation through in-depth studies. Drug-likeness analysis was performed to assess the phytochemicals drug-like properties. Two promising phytochemicals, 3,4-dicaffeoylquinic acid and Chlorogenic acid, were identified, both exhibiting high docking affinity and unique binding site interactions compared to the established PPARγ full agonist, rosiglitazone. Molecular dynamics simulations of 100 ns were conducted to examine the stability of the complexes formed by both compounds within the PPARγ active site, and their dynamic behavior was compared to the reference structure of PPARγ alone and with rosiglitazone. Binding free energy calculations demonstrated that 3,4-dicaffeoylquinic acid and Chlorogenic acid exhibited higher binding free energy than the reference agonist, suggesting their potential as candidates for experimental validation in future drug discovery efforts targeting PPARγ for the treatment of T2D and metabolic syndrome.

Keywords

PPARγ, Moroccan phyto-chemicals, virtual screening, molecular dynamic simulation, energy free binding calculation.

Citation

Elkhattabi et al. Bioinformation 19(7): 795-805 (2023)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.