Synthesis and bioevaluation of novel theophylline-dendrimer conjugates

MEDI 70

Xingyi Yang, yang1x@cmich.edu1, Minghui Chai, minghui.chai@cmich.edu1, Ping Zhou, PZHOU@PATH.WUSTL.EDU2, and Shengxiang Qiu, sqiu@wuchem.wustl.edu3. (1) Department of Chemistry, Central Michigan University, Mt. Pleasant, MI 48859, (2) Department of Physiology, Washington University, St. Louis, MO 63130, (3) Department of Chemistry, Washington University, One Brooking drive, St. Louis, MO 63130
Theophylline, a common drug for the treatment of asthma and chronic obstructive pulmonary disease, was found to be able to treat cancer in normal therapeutic doses. In this work, we first successfully conjugate multiple theophylline drug entities on the periphery of poly(propyleneimine) (PPI) dendrimers. The PPI dendrimers used for the synthesis are from generation 1 to 3 (PPI-1, PPI-2 and PPI-3). The novel drug-dendrimer conjugates have been characterized using UV-Vis, high resolution NMR and MALDI-TOF-MS. The solubility tests on these dendrimer-drug conjugates indicate that the water solubility of the conjugates per drug unity is increased in comparison with the drug alone. MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay was also performed on Hep G2 cells for anticancer testing of these novel drug-dendrimer conjugates. Comparing theophylline itself, a better synergistic effect with cisplatin on the induction of cancer cell death was observed for the drug-dendrimer conjugates, which may permit a reduction in the dose and toxicity of cisplatin in cancer treatment.

 

General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006