- Research and development of phospha sugar anti-cancer agents with anti-leukemic activity
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We have synthesized three deoxybromophospha sugar analogues, 4-bromo-3-methyl-l-phenyl-2-phospholene 1-oxide (MBMPP (2)), 2,3-dibromo-3-methyl-l-phenylphospholane 1-oxide (DBMPP (3)), and 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide (TBMPP (4)), by the reaction of 3-methyl-l-phenyl-2-phospholene 1-oxide (lb) and/or 2 with bromine, and investigated their potentials as anti-leukemic agents against human leukemia cell lines of K562 and U937. Cells' growth inhibition was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) in vitro assay. All agents showed inhibitory effects on leukemia cell proliferation, indicating that inhibition appeared to be dependent on number of bromine substituent in the heterocyclic structure. Further, the phospha sugar derivatives did not show any inhibitory effects on normal cell proliferation. These agents may facilitate the development of new strategies in molecular targeting anti-leukemic therapy.
- Yamashita, Junko,Suyamab, Takuya,Asai, Kazuhide,Yamada, Manabu,Niimi, Taishi,Fujie, Michio,Nakamura, Satoki,Ohnishi, Kazunori,Yamashita, Mitsuji
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- Preparation of phospha sugar analogues and their evaluation as novel molecular targeting anticancer agents
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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
- Tsunekawa, Kenji,Yamashita, Mitsuji,Fujie, Michio,Niimi, Taishi,Suyama, Takuya,Asai, Kazuhide,Ito, Satoru,Yamashita, Junko,Yamada, Manabu,Ozaki, Nobuhisa,Nakamura, Satoki
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- Novel Multiple Type Molecular Targeted Antitumor Agents: Preparation and Preclinical Evaluation of Low-Molecular-Weight Phospha Sugar Derivatives
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Phospha sugar derivatives of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide and 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide were synthesized from 2-phospholenes and evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide method against leukemia cell lines, and then characterized by cell cycle analysis, Western blot analysis, and molecular docking simulation. Phospha sugar derivatives were revealed to be potential antitumor agents against leukemia cell lines such as U937 and K562. Cell cycle analysis indicated that phospha sugar derivatives induced apoptoses. Western blot analyses against U937 showed that phospha sugar derivatives regulate many mitotic regulators in cell cycle. Results of molecular docking simulation suggested that phospha sugar derivatives enter the pockets present in cell cycle and apoptosis-related proteins.
- Makita, Reiko,Yamashita, Mitsuji,Yamaoka, Mayumi,Fujie, Michio,Nakamura, Satoki,Oshikawa, Tatsuo,Yamashita, Junko,Yamada, Manabu,Asai, Kazuhide,Suyama, Takuya,Kondo, Mitsuru,Hasegawa, Hiroko,Okita, Yoshimitsu,Hirakawa, Kazutaka,Toda, Mitsuo,Ohnishi, Kazunori,Sugimura, Haruhiko
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p. 733 - 740
(2016/01/15)
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- Research on phospha sugar analogues to develop novel multiple type molecular targeted antitumor drugs against various types of tumor cells
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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- phenylphospho
- Makita, Reiko,Yamashita, Mitsuji,Fujie, Michio,Yamaoka, Mayumi,Kiyofuji, Keita,Yamada, Manabu,Yamashita, Junko,Tsunekawa, Kenji,Asai, Kazuhide,Suyama, Takuya,Toda, Mitsuo,Tanaka, Yasutaka,Sugimura, Haruhiko,Magata, Yasuhiro,Ohnishi, Kazunori,Nakamura, Satoki
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p. 213 - 223
(2013/07/11)
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