Synthesis, in vitro, and in vivo evaluation of novel functionalized quaternary ammonium curcuminoids as potential anti-cancer agents.

Abstract

Novel functionalized quaternary ammonium curcuminoids have been synthesized from piperazinyl curcuminoids and Baylis-Hillman reaction derived allyl bromides. These molecules are found to be highly water soluble with increased cytotoxicity compared to native curcumin against three cancer cell lines MIAPaCa-2, MDA-MB-231, and 4T1. Preliminary in vivo toxicity evaluation of a representative curcuminoid 5a in healthy mice indicates that this molecule is well tolerated based on normal body weight gains compared to control group. Furthermore, the efficacy of 5a has been tested in a pancreatic cancer xenograft model of MIAPaCa-2 and has been found to exhibit good tumor growth inhibition as a single agent and also in combination with clinical pancreatic cancer drug gemcitabine.

• Authors: Lucas N Solano, Grady L Nelson, Conor T Ronayne, Erica A Lueth, Melissa A Foxley, Sravan K Jonnalagadda, Shirisha Gurrapu, Venkatram R Mereddy
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 24 Pg. 5777-80 (Dec 15 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26561365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Quaternary Ammonium Compounds
• Curcumin

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology, therapeutic use)
• Body Weight (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Curcumin (chemistry, pharmacology, therapeutic use)
• Female
• Humans
• Mice
• Mice, Nude
• Neoplasms (drug therapy)
• Quaternary Ammonium Compounds (chemistry)
• Transplantation, Heterologous