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New nicotinic acid-based 3,5-diphenylpyrazoles: design, synthesis and antihyperlipidemic activity with potential NPC1L1 inhibitory activity.

Mai E ShomanMoustafa O AboelezMontaser Sh A ShaykhonSanaa A AhmedGamal El-Din A Abuo-RahmaOmar M Elhady
Published in: Molecular diversity (2020)
Nicotinic acid hydrazide was incorporated into new 4,5-dihydro-5-hydroxy-3,5-diphenylpyrazol-1-yl derivatives. Compounds 6a-h were synthesized, and their antihyperlipidemic activity was evaluated in high cholesterol diet-fed rat model. Compounds 6e, 6f were found to decrease the levels of serum total cholesterol by 14-19% compared to control group. Total triglycerides were also reduced by 24-28% and LDL cholesterol by 16%. As expected from parent niacin, compounds 6e and 6f caused an elevation of HDL cholesterol by 33-41%. Docking study supported the ability of designed compounds to block NPC1L1 active site in a manner similar to that observed with ezetimibe.
Keyphrases
  • low density lipoprotein
  • physical activity
  • weight loss
  • risk assessment
  • small molecule
  • protein protein
  • structure activity relationship