Multifunctional Cinnamic Acid Derivatives

Molecules. 2017 Jul 25;22(8):1247. doi: 10.3390/molecules22081247.

Abstract

Our research to discover potential new multitarget agents led to the synthesis of 10 novel derivatives of cinnamic acids and propranolol, atenolol, 1-adamantanol, naphth-1-ol, and (benzylamino) ethan-1-ol. The synthesized molecules were evaluated as trypsin, lipoxygenase and lipid peroxidation inhibitors and for their cytotoxicity. Compound 2b derived from phenoxyphenyl cinnamic acid and propranolol showed the highest lipoxygenase (LOX) inhibition (IC50 = 6 μΜ) and antiproteolytic activity (IC50 = 0.425 μΜ). The conjugate 1a of simple cinnamic acid with propranolol showed the higher antiproteolytic activity (IC50 = 0.315 μΜ) and good LOX inhibitory activity (IC50 = 66 μΜ). Compounds 3a and 3b, derived from methoxylated caffeic acid present a promising combination of in vitro inhibitory and antioxidative activities. The S isomer of 2b also presented an interesting multitarget biological profile in vitro. Molecular docking studies point to the fact that the theoretical results for LOX-inhibitor binding are identical to those from preliminary in vitro study.

Keywords: antiproteolytic activity; cinnamic acids; lipoxygenase inhibitors; multitarget.

MeSH terms

  • Animals
  • Cell Line
  • Cinnamates* / chemical synthesis
  • Cinnamates* / chemistry
  • Glycine max
  • Lipoxygenase / chemistry*
  • Lipoxygenase Inhibitors* / chemical synthesis
  • Lipoxygenase Inhibitors* / chemistry
  • Mice
  • Propranolol* / analogs & derivatives
  • Propranolol* / chemical synthesis
  • Propranolol* / chemistry
  • Protease Inhibitors* / chemical synthesis
  • Protease Inhibitors* / chemistry
  • Soybean Proteins* / antagonists & inhibitors
  • Soybean Proteins* / chemistry

Substances

  • Cinnamates
  • Lipoxygenase Inhibitors
  • Protease Inhibitors
  • Soybean Proteins
  • cinnamic acid
  • Propranolol
  • Lipoxygenase