A Review on Structurally Diversified Synthesized Molecules as Monoacylglycerol Lipase Inhibitors and their Therapeutic uses

Curr Drug Res Rev. 2022;14(2):96-115. doi: 10.2174/2589977514666220301111457.

Abstract

Monoacylglycerol is a metabolic key serine hydrolase engaged in the regulation of the signalling network system of endocannabinoids, which is associated with various physiological processes like pain, inflammation, feeding cognition, and neurodegenerative diseases like Alzheimer's and Parkinson's disease. The monoacylglycerol was also found to act as a regulator and the free fatty acid provider in the proliferation of cancer cells as well as numerous aggressive tumours such as colorectal cancer, neuroblastoma, and nasopharyngeal carcinoma. It also played an important role in increasing the concentration of specific lipids derived from free fatty acids like phosphatidic acid, lysophosphatidic acid, sphingosine-1-phosphate, and prostaglandin E2. These signalling lipids are associated with cell proliferation, survival, tumour cell migration, contribution to tumour development, maturation, and metastases. In this study, we present a review on structurally diverse MAGL inhibitors, their development, and their evaluation for different pharmacological activities.

Keywords: 2-arachidonoylglycerol; Amino acids; arachidonic acid; endocannabinoid system; enzyme; monoacylglycerol lipase; monoacylglycerol lipase inhibitors; receptors.

Publication types

  • Review

MeSH terms

  • Endocannabinoids / metabolism
  • Enzyme Inhibitors* / pharmacology
  • Enzyme Inhibitors* / therapeutic use
  • Humans
  • Monoacylglycerol Lipases* / antagonists & inhibitors
  • Monoacylglycerol Lipases* / metabolism
  • Monoglycerides / therapeutic use
  • Neoplasms* / drug therapy

Substances

  • Endocannabinoids
  • Enzyme Inhibitors
  • Monoglycerides
  • Monoacylglycerol Lipases