Preparation of Phospha Sugar Analogues and Their Evaluation as Novel Molecular Targeting Anticancer Agents

Abstract

Phospha sugars were prepared by a novel synthetic route starting from phosphorus heterocyclic compounds, 2-phospholenes. The anhydro- and deoxy-phospha sugar derivatives have been revealed to have potential anticancer activities against human leukemia of K562 and U937 cell lines. In this article, deoxybromophospha sugars with different numbers of bromo substituents were prepared, and their anticancer activities were evaluated by MTT method. The order of the activities depending on the number of bromo substituent was first revealed, and trideoxytribromotetrofuranose type phospha sugar [2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide (4: TBMPPAO)] was the most active among these phospha sugars prepared. Diasteromers of dideoxydibromotetrofuranose-type phospha sugar [2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (2: DBMPPAO)] were separated into four components, and the structure as well as the character of each component was assigned by spectral and chromatographic data as well as by MTT method.The deoxybromophospha sugars have higher antileukemia activity than Gleevec against U937 cells.

Keywords:

• Antileukemia
• deoxybromophospha sugars
• MTT in vitro evaluation
• phosphorus heterocycles

Acknowledgments

The authors greatly acknowledge financial support by the Satellite Shizuoka and the Headquarters of Japan Science and Technology Agency (JST); Grants-in-Aid for Scientific Research by Japan Society for the Promotion of Science (JSPS), the Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT); and the Ministry of Health, Labour and Welfare, Japan (MHLW).