Bioisosteric Analogues of Cinnamic Acid as Effective Neuroprotectors

  • M.E. Neganova Institute of Physiologically Active Substances, Russian Academy of Sciences, 1 Severny proezd, Chernogolovka, 142432 Russia
  • V. Semenov Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky av., Moscow, 119991 Russia
  • M. Semenova Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova str., Moscow, 119334 Russia
  • O.M. Redkozubova OOO Neurobotics, Directions 4922, 4-2, Southern Industrial Area, Zelenograd, 124498 Russia
  • Yu.R. Aleksandrova Ivanovo State University, School of Biology and Chemistry, Department of General Biology and Physiology, 136 Lenina av., Ivanovo, Russia
  • E.A. Lysova Institute of Physiologically Active Substances, Russian Academy of Sciences, 1 Severny proezd, Chernogolovka, 142432 Russia
  • S.G. Klochkov Institute of Physiologically Active Substances, Russian Academy of Sciences, 1 Severny proezd, Chernogolovka, 142432 Russia
  • E.F. Shevtsova Institute of Physiologically Active Substances, Russian Academy of Sciences, 1 Severny proezd, Chernogolovka, 142432 Russia
Keywords: cinnamic acid, neuroprotectors, neurodegenerative diseases, mitochondria, antioxidants

Abstract

Compounds that act on mitochondrial functions are considered as promising drugs for the treatment of neurodegenerative diseases and age-related dementias. As a basis for the creation of such potential drugs, bioisosteric cinnamic acid analogs and polymethoxybenzene derivatives were selected. Derivatives of cinnamic acid have a wide range of biological activities, which can be important for drugs aimed at the treatment of neurodegenerative diseases, in particular Alzheimer′s disease. In this work, the neuroprotective activity of bioisosteric cinnamic acid analogs and polymethoxybenzene derivatives was studied. Among the compounds studied, lead substances 3, 4, and 7 have been identified. These compounds show no intrinsic toxicity and have a neuroprotective effect on the cellular model of neurodegeneration associated with calcium stress. The mechanism of their cytoprotective activity is probably due to the influence on mitochondrial functions, because these compounds effectively suppress the calcium-induced process of mitochondrial permeability jump. In addition, one of the substances investigated (7) has antioxidant properties, showing the ability to inhibit lipid peroxidation (LPO) of rat brain homogenate, which may be an additional mechanism of neuroprotective effect. The data obtained make it possible to recommend the investigated substances as a basis for the creation of effective neuroprotective drugs capable of influencing early stages of the development of neurodegenerative diseases.

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Published
2018-07-16
Section
Experimental Research