Insights into the promising prospect of medicinal chemistry studies against neurodegenerative disorders

Chem Biol Interact. 2023 Mar 1:373:110375. doi: 10.1016/j.cbi.2023.110375. Epub 2023 Feb 3.

Abstract

Medicinal chemistry is an interdisciplinary field that incorporates organic chemistry, biochemistry, physical chemistry, pharmacology, informatics, molecular biology, structural biology, cell biology, and other disciplines. Additionally, it considers molecular factors such as the mode of action of the drugs, their chemical structure-activity relationship (SAR), and pharmacokinetic aspects like absorption, distribution, metabolism, elimination, and toxicity. Neurodegenerative disorders (NDs), which are defined by the breakdown of neurons over time, are affecting an increasing number of people. Oxidative stress, particularly the increased production of Reactive Oxygen Species (ROS), plays a crucial role in the growth of various disorders, as indicated by the identification of protein, lipid, and Deoxyribonucleic acid (DNA) oxidation products in vivo. Because of their inherent nature, most biological molecules are vulnerable to ROS, even if they play a role in metabolic parameters and cell signaling. Due to their high polyunsaturated fatty acid content, low antioxidant barrier, and high oxygen uptake, neurons are particularly vulnerable to oxidation by nature. As a result, excessive ROS generation in neurons looks especially harmful, and the mechanisms associated with biomolecule oxidative destruction are several and complex. This review focuses on the formation and management of ROS, as well as their chemical characteristics (both thermodynamic and kinetic), interactions, and implications in NDs.

Keywords: Medicinal chemistry; Neurodegenerative disorders; Neurons; ROS; Structure-activity relationship.

Publication types

  • Review

MeSH terms

  • Chemistry, Pharmaceutical*
  • Humans
  • Neurodegenerative Diseases* / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Reactive Oxygen Species / metabolism

Substances

  • Reactive Oxygen Species