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Syntheses and Evaluations of Antitumor and Antiangiogenic Compounds Conjugated with 5-Fluorouracil and Ascorbic Acid

Department of Polymer Science and Engineering Pusan National University, Busan 609-735, Korea

Bo-Gyeong Kim

Department of Polymer Science and Engineering Pusan National University, Busan 609-735, Korea

Chang-Sik Ha

Department of Polymer Science and Engineering Pusan National University, Busan 609-735, Korea

Ildoo Chung

Department of Polymer Science and Engineering Pusan National University, Busan 609-735, Korea, idchung{at}pusan.ac.kr

Dong Xie

Department of Biomedical Engineering, Purdue School of Engineering and Technology, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, USA

The new multifunctional antitumor conjugates containing ascorbic acid and 5-fluorouracil (5-FU) were synthesized from bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, ascorbic acid and/or a chain spacer, followed by condensation with 5-FU. The synthesized conjugates were identified by ¹H and ¹³C NMR spectroscopies and elemental analysis. The in vitro cytotoxicities of these conjugates were determined and their antitumor activity was evaluated. The IC₅₀ values (drug concentration for 50% inhibition of tumor growth) indicated that the synthesized conjugates were better inhibitors against cancer cells and were lower in cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined against mice bearing the sarcoma 180 tumor cells. The life spans (T/C) of mice treated with the conjugates were higher than for the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity, based on the embryo chorioallantoic membrane assay.

Key Words: antitumor activity • drug conjugates • 5-fluorouracil • 5-fluorouracil conjugates • ascorbic acid • in vitro cytotoxicity • antiangiogenesis.

Journal of Bioactive and Compatible Polymers, Vol. 23, No. 5, 473-489 (2008)
DOI: 10.1177/0883911508095505


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