Lipid lowering activity of novelN-(benzoylphenyl)pyridine-3-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats

Abstract

This research opens the door for new potential antihyperlipidemic compounds derived from nicotinic acid that need further optimization of their biological activities.

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

“…C12 lacks such interaction due to steric 3‐methyl substituent. These suggestions are in concordance with previously obtained results on N ‐(benzoylphenyl)pyridine‐3‐carboxamide , where activities were decreased in general by switching the amide linker from positions 3 or 4 to position 2.…”

“…Based on the previous acute toxicity study for a related compounds ( N ‐(benzoylphenyl)pyridine‐3‐carboxamide derivatives), doses of 20–100 mg/kg were considered to be safe for the evaluation of antihyperlipidemic effect . In this study, a dose–response curve was established at five different doses for C6 compound (20, 30, 50, and 100 mg/kg) to evaluate the potential antihypelipidemic effect of each dose.…”

“…The selection of the experimental dose was based on previous acute toxicity study that was conducted by the same research team on related compounds “ N ‐(benzoylphenyl)pyridine‐3‐carboxamide derivatives” at doses from 200 mg/kg to 1000 mg/kg on Balb/c mice .…”

“…Although nicotinic acid has been historically used for its lipid‐lowering and antioxidant effect to prevent cardiovascular diseases and atherosclerosis, the associated multiple side effects have marred its popularity . Therefore, tremendous efforts were employed to synthesize and evaluate different nicotinic acid derivatives for the treatment of hyperlipidemia with improved anti‐atherogenic effect and with less adverse events .…”

“…Previously, our laboratory has reported the synthesis and evaluation for antihyperlipidemic activity of nicotinic acid derivatives, N ‐(benzoylphenyl)pyridine‐3‐carboxamide analogs . In this study, isonicotinic acid (which is an isomer of nicotinic acid) was used as our starting point to synthesize novel isonicotinic carboxamide derivatives bearing the benzophenone unit of the fenofibrate drug (Fig.…”