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

Bioorg Med Chem Lett. 2015 Dec 15;25(24):5777-80. doi: 10.1016/j.bmcl.2015.10.061.

Lucas N Solano ¹, Grady L Nelson ², Conor T Ronayne ¹, Erica A Lueth ¹, Melissa A Foxley ¹, Sravan K Jonnalagadda ², Shirisha Gurrapu ², Venkatram R Mereddy ³

Affiliations

1 Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN 55812, United States.
2 Integrated Biosciences Graduate Program, University of Minnesota, Duluth, MN 55812, United States.
3 Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN 55812, United States; Integrated Biosciences Graduate Program, University of Minnesota, Duluth, MN 55812, United States; Department of Pharmacy Practice & Pharmaceutical Sciences, University of Minnesota, Duluth, MN 55812, United States. Electronic address: [email protected].

PMID: 26561365 DOI: 10.1016/j.bmcl.2015.10.061

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.

Keywords

Baylis–Hillman derived allyl bromides; Breast cancer; Curcuminoids; Pancreatic cancer; Quaternary ammonium salts.

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