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The synthesis and antitumor activity evaluation of new branched phospha sugars, especially deoxybromophospha sugar derivatives or bromophospholanes of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (DBMPP: 3) and 2,3,4-tribromo-3-methyl-1- phenylphospholane 1-oxide (TBMPP: 4), against various types of leukemia cell lines as well as the results of the mechanistic studies for characterizing and developing the novel multiple type molecular targeted antitumor agents are reported in this paper. DBMPP and TBMPP were prepared from 1-phenyl-3-methyl-2-phospholene 1-oxide (1). The isomer mixture of phospha sugars prepared were evaluated as novel antitumor agents by MTT in vitro method. DBMPP and TBMPP were characterized by flow cytometry and Western blot analysis and were revealed to be potential antitumor agents against leukemia cell lines of K562 (one type of leukemia cell lines of CML) and U937 (one type of leukemia cell lines of AML) as well as against the various types of leukemia cell lines and al...

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 met...

The synthesis of new phospha sugar analogues or phosphorus heterocycles and their biological activities as novel anticancer agents are reported in this article. A 1,2-dibromo-1,2-dideoxy phospha sugar derivative, 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide (2), was prepared from 1-phenyl-3-methyl-2-phospholene 1-oxide (1), and the yield and ratio of diastereomers 2a to 2d were changed by a catalyst such as manganese(IV) oxide and manganese(II) bromide. The antitumor activities of the mixture of dibromides 2 and the separated diastereomeric components 2a to 2d of the dibromides were evaluated by MTT in vitro method against the human leukemia cell lines of K562 and U937. The results showed that all of the diastereomers 2a to 2d as well as the diastereomer mixture exert excellent anticancer activity, and moreover, among them, diastereomer 2d showed the highest antitumor activity. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silico...

4-Bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide ( 3c ) was first synthesized from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide ( 2c ) by a bromo-radical substitution reaction occurred at C-4 position by N -bromosuccinimide and 2,2′-azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti-proliferative effect on U937 cells evaluated by MTT in vitro methods and was much more efficient than that of Gleevec®, which is known as a molecule targeting chemotherapeutical agent. The substitution of 2-phospholenes at C-3 and C-4 position with methyl groups as well as 4-bromo substituent suggests a good anti-proliferative effect.