Synthesis and characterization of N-hexylamino phenoxazines as potential anticancer drugs

MEDI 311

Bharathalaxmi Pulluru, B-Pulluru@wiu.edu1, Parimala B. Hanumesh, PB-hanumesh@wiu.edu1, Kuntebommanahalli N. Thimmaiah2, and Netkal M. Made Gowda, GN-Made@wiu.edu1. (1) Department of Chemistry, Western Illinois University, 1 University Circle, Macomb, IL 61455, (2) Department of Molecular Pharmacology, St. Jude Children’s Research Hospital, Memphis, TN 38105
Phenoxazines are known for anti-multidrug resistance (MDR) activities. We hypothesize that by increasing the alkyl side chain length, the derivative's potency as anticancer agent will increase. We are synthesizing and characterizing a series of seven hydrophobic N-substituted phenoxazines with a six carbon alkyl side chain and different amino functionalities. Each synthesis is based on the ability of N-(10-chloroalkyl)phenoxazines to undergo iodide catalyzed nucleophilic substitution reactions with secondary amines such as N,N-diethylamine, N-diethanolamine, pyrrolidine, piperidine, morpholine, thiomorpholine, and (â-hydroxyethyl)piperazine. The products are characterized by UV, IR, 1H and 13C NMR, mass spectral and elemental data. The lipophilicities are to be determined. The purified compounds also are to be evaluated for anticancer activity.

In this study, in addition to the synthesis of seven hexylamino phenoxazine derivatives, we plan to determine their IC50 and screen them for inhibition of the phosphorylation of AKT and downstream targets.

Acknowledgement: We thank the NIH (AREA grant # 5-20860) for support

 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007