Lipid Lowering Oxopropanylindole Hydrazone Derivatives with Antioxidant and Anti-hyperglycemic Activity

Curr Top Med Chem. 2018;18(26):2256-2265. doi: 10.2174/1568026619666181220112903.

Abstract

A series of substituted oxopropanylindole hydrazone derivatives was synthesized and evaluated for anti-oxidant and anti-dyslipidemic activity. Of the 12 tested, 3 compounds (6c, 7b and 7d) showed good anti-oxidant activity, compound 6c attenuated LDL oxidation by 32%. The compounds 6c and 7d also showed good anti-dyslipidemic activity by reducing serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). These two compounds were further evaluated for antiadipogenic and anti-hyperglycemic activity, where 6c showed 44% reduction in lipid accumulation and 20.5% and 24.3% reduction in blood glucose at 5h and 24h respectively, as compared to standard drug metformin. Thus, compounds 6c and 7d with balanced anti-oxidant and anti-dyslipidimic activities may be excellent candidates for lead optimization and drug development for the treatment of metabolic disorders.

Keywords: Anti-dyslipidemic; Anti-hyperglycemic; Anti-oxidant; Atherosclerosis; Hydrazone derivatives; Lipid..

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / therapeutic use*
  • Blood Glucose / drug effects
  • Cells, Cultured
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry
  • Hydrazones / therapeutic use*
  • Hydroxyl Radical / antagonists & inhibitors
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / therapeutic use*
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / therapeutic use*
  • Lipoproteins, LDL / chemistry
  • Lipoproteins, LDL / therapeutic use*
  • Male
  • Mice
  • Oxygen / chemistry
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antioxidants
  • Blood Glucose
  • Hydrazones
  • Hypoglycemic Agents
  • Indoles
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Hydroxyl Radical
  • Oxygen