New N-substituted phenoxazines as specific inhibitors of Akt in cancer cells

MEDI 310

Parimala B. Hanumesh, PB-hanumesh@wiu.edu1, Bharathalaxmi Pulluru, B-Pulluru@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
Drug resistance is always a major obstacle in the clinical treatment of cancer. Several pharmacological agents including some phenoxazines have been shown to reverse multi drug resistance in vitro and there is still a need to identify more potent, more specific, and less toxic modulators for clinical use. We hypothesize that by increasing the alkyl side chain length, the phenoxazine derivative's potency as anticancer agent will be enhanced.

In this project, we have synthesized a series of N-substituted phenoxazines with pentylamino and hexylamino side chains and are screening them to find out whether they are more/less potent than the previously reported derivatives. In order to predict the mechanism of anticancer action, cell screening for Akt inhibition is being started in Rhabdomyosarcoma cell lines (Rh1 and Rh30). Furthermore, to determine the inhibitory concentration of each drug, a standard growth inhibition assay is being performed.

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