Nipecotic acid as potential lead molecule for the development of GABA uptake inhibitors; structural insights and design strategies.

Karanvir Singh, Piyush Kumar, Rohit Bhatia, Vipasha Mehta, Bhupinder Kumar, Md Jawaid Akhtar

European journal of medicinal chemistry 2022 Apr 15

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Gamma-Aminobutyric Acid (GABA) inhibitory neurotransmitter departs an energetic role in brain signalling system. Levels of GABA in the brain influence human behaviour, diminishes in the degree of GABA can cause seizures, depression, Parkinson's. To put it plainly, it plays a basic part in the significant issues of mind. It is exceptionally important to cure the issues linked to GABA. Writing overview proposed that nipecotic acid is an intense GABA reuptake inhibitor. This scaffold is likewise present in one of the promoted anticonvulsant drugs 'Tiagabine'. Tiagabine is only drug in the market which works through this mechanism however the medication is regulated with one more prescription for the synergistic impact. Nipecotic acid has several disadvantages such as it can't cross the blood-brain barrier because of its hydrophilic and zwitterionic nature. To avoid this problem nipecotic acid scaffold hybrids with the different aromatic groups can enhance the physical (lipophilicity) as well as biological properties of the resultant compound. So, there is a dire requirement for compounds that work through this mechanism. Several medicinal chemists and researchers are already working in this field and developed outstanding newer molecules. This review article compiles these developed new hybrids along with design strategies, structure-activity relationship, and biological activity as well as in silico studies. This review also demonstrates the synthesis of nipecotic acid and the core mechanism through which nipecotic acid acts as a GABA reuptake inhibitor. Copyright © 2022 Elsevier Masson SAS. All rights reserved.

Citation

Karanvir Singh, Piyush Kumar, Rohit Bhatia, Vipasha Mehta, Bhupinder Kumar, Md Jawaid Akhtar. Nipecotic acid as potential lead molecule for the development of GABA uptake inhibitors; structural insights and design strategies. European journal of medicinal chemistry. 2022 Apr 15;234:114269