Ginger (Zingiber officinale) components as alternative for inhibition of the human dopamine receptor D2: a computational approach

ABSTRACT

Human dopamine receptor D2 (DRD2) is one of the molecular targets for the drug development against some neurological disorders playing a vital role in the dopamine equilibrium in the brain. Atypical drugs like Risperidone, used against schizophrenia, with proven efficacy in reducing the extra pyramidal symptoms of this disease, act as agonist inhibitors of DRD2. However, these drugs are not capable of curing schizophrenia, there is still room for the drug development against this disease. We investigated here the ability of 12 components of the Ginger (Zingiber officinale) extract, known since ancient times to be effective against various diseases including neurological ones, for their molecular interactions with the human DRD2 receptor. Among all the amino acids participating in the binding process, we found that Trp386 plays a vital role, since it fixes the ligands by pi-stacking while Asp114 binds them through a H-bond. This knowledge is important since it supports the traditional use of this plant in natural medicine and also serves as a starting point for the design of drugs derived from these natural components.

KEYWORDS:

• Medicinal chemistry
• neurological diseases
• ginger active principles
• dopamine receptor D2
• molecular modelling

Acknowledgements

The authors thank the Faculty of Technology of the State University of Rio de Janeiro (FAT-UERJ) for the facilities provided, the Research Support Foundation of the State of Rio de Janeiro - FAPERJ for the grant projects ARC-2019 and E-26/010.001628/2016 and E-02/202.961/2017 and Conselho Nacional de Pesquisa (CNPq), grant number 308225/2018–0. Authors especially thanks the free software developers (Ubuntu, Gromacs, AutoDocking Vina, g_mmpbsa, VMD, Qtiplot, Python, Gimp and Libre Office), without whom this work would not be possible. This work was also supported by the University of Hradec Králové.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors thank the Faculty of Technology of the State University of Rio de Janeiro (FAT-UERJ) for the facilities provided, the Research Support Foundation of the State of Rio de Janeiro - FAPERJ for [grant projects ARC-2019 and E-26/010.001628/2016 and E-02/202.961/2017] and Conselho Nacional de Pesquisa (CNPq) [grant number 308225/2018-0].