Synthetic Studies

New Conjugates of Antitumor Antibiotic Doxorubicin with Water-Soluble Galactomannan: Synthesis and Biological Activity

A. N. Tevyashova¹, E. N. Olsufyeva^1#, M. N. Preobrazhenskaya¹, A. A. Klyosov², E. Zomer² and D. Platt²

^#Phone: (495) 245-37-53; fax: (495) 245-02-95; e-mail: eolsufeva@list.ru

¹Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, ul. Bol’shaya Pirogovskaya 11, Moscow, 119021, Russia;
²Pro-Pharmaceuticals, 7 Wells Avenue, Newton, MA 02459, USA

Received: April 7, 2006; in final form: May 24, 2006

Abstract. New water-soluble conjugates in the form of Schiff bases (DGM-1 and DGM-2) were prepared by the interaction of water-soluble periodate-oxidized galactomannan with doxorubicin or N-(L-lysyl)doxorubicin, respectively. The water-soluble galactomannan (DAVANAT®, a commercial product of Pro-Pharmaceuticals company) was obtained by partial acidic hydrolysis of high-molecular-mass galactomannan from Cyamopsis tetragonoloba (guar gum) seeds. The conjugate stability was studied in aqueous solutions. The DGM-1 anti-proliferative activity was comparable with that of doxorubicin on three models: cell lines of murine melanoma B16-F1 and human breast cancer MCF-7 (HTB-22) and human colon cancer HT-29 (HTB-38). DGM-2 was poorly active in all the three tests. DGM-1 can thus be regarded as a high-molecular-mass depot form of doxorubicin.

Key words: antiproliferative activity, doxorubicin conjugates, 1,4-β-D-galactomannan

Russian Journal of Bioorganic Chemistry 2007, 33 (1): 139-145