Pharmacological Evaluation of Novel Isonicotinic Carboxamide Derivatives as Potential Anti-Hyperlipidemic and Antioxidant Agents

Arch Pharm (Weinheim). 2017 Oct;350(10). doi: 10.1002/ardp.201700024. Epub 2017 Aug 24.

Abstract

Hyperlipidemia and oxidative stress have been implicated as contributing factors to the development of atherosclerosis and cardiovascular diseases (CVDs). Currently, a large number of antihyperlipidemic medications are conveniently available in the market. Nonetheless, the majority of antihyperlipidemics lack the desired safety and efficacy. Thus, the present study was undertaken to evaluate the potential effect of novel N-(benzoylphenyl)pyridine-4-carboxamide and N-(9,10-dioxo-9,10-dihydroanthracenyl)pyridine-4-carboxamide derivatives in controlling hyperlipidemia and oxidative stress using the Triton WR-1339-induced hyperlipidemic rat model for antihyperlipidemic activity and the DPPH radical scavenging assay for antioxidant activity. This study revealed the antihyperlipidemic activities of some of the newly synthesized, novel carboxamide derivatives, mainly C4 and C12 (p < 0.05). The majority of the compounds displayed a relatively low or no DPPH radical scavenging effect, with C20 possessing the best radical scavenging effect (22%) among all. This research opens the door for new potential antihyperlipidemic compounds derived from isonicotinic acid. N-(3-Benzoylphenyl)pyridine-4-carboxamide (C4) was found to have promising lipid-lowering and antioxidant effects, which may create a protective effect against CVDs, by reducing the LDL-C levels and diminishing the generation of reactive oxygen species.

Keywords: Antihyperlipidemic; Antioxidant; Isonicotinic acid; Triton WR-1339.

MeSH terms

  • Animals
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Disease Models, Animal
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Hyperlipidemias / drug therapy
  • Hypolipidemic Agents / chemical synthesis
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacology*
  • Isonicotinic Acids / chemical synthesis
  • Isonicotinic Acids / chemistry
  • Isonicotinic Acids / pharmacology*
  • Male
  • Oxidative Stress / drug effects
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Hypolipidemic Agents
  • Isonicotinic Acids
  • Pyridines
  • Reactive Oxygen Species