Synthesis, in vitro, and in vivo evaluation of novel functionalized quaternary ammonium curcuminoids as potential anti-cancer agents. Issue 24 (15th December 2015)

• Record Type: Journal Article
• Authors: Solano, Lucas N.; Nelson, Grady L.; Ronayne, Conor T.; Lueth, Erica A.; Foxley, Melissa A.; Jonnalagadda, Sravan K.; Gurrapu, Shirisha; Mereddy, Venkatram R.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 24(2015)
• Page Start: 5777
• Page End: 5780
• Publication Date: 2015-12-15
• Subjects: Baylis–Hillman derived allyl bromides -- Quaternary ammonium salts -- Curcuminoids -- Breast cancer -- Pancreatic cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.10.061
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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 curcuminoid5a in healthy mice indicates that this molecule is well tolerated based on normal body weight gains compared to control group. Furthermore, the efficacy of5a 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.