Design and synthesis of glycoside inhibitors of glioma and melanoma growth.

Abstract

An N-acetylglucosaminide derivative with a pentaerythritol substituent at position C-6 was previously synthesized and shown to inhibit neural tumor growth. Now, we report the preparation of a series of new synthetic compounds introducing systematic changes in the nature, polarity, and size of the sugar substituents. The antimitotic activity of the new compounds was tested on cultured rat (C6) and human (U-373) glioma lines and on a human melanoma line (A-375). The antimitotic and antitumoral activity of the new compounds on glioma cell lines increased up to 2 orders of magnitude with respect to the parent compound or was abolished, permitting a detailed structure-function analysis of the new antitumorals. One of the glycosides inhibited melanoma division with an ID50 below the micromolar range.

• Authors: Isabel García-Alvarez, Guillermo Corrales, Ernesto Doncel-Pérez, Ana Muñoz, Manuel Nieto-Sampedro, Alfonso Fernández-Mayoralas
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 2 Pg. 364-73 (Jan 25 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17228879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Glycosides

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Design
• Drug Screening Assays, Antitumor
• Glioma
• Glycosides (chemical synthesis, chemistry, pharmacology)
• Humans
• Melanoma
• Rats
• Structure-Activity Relationship