- 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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- Synthesis of Some 1-aryl-2,3-dibromophospholanes as novel anti-cancer agents
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Novel phosphorus heterocyclic compounds, 3-methyl-1-(3-bromophenyl as well as some 3-substituted phenyl)-2- phospholene 1-oxides (1d as well as 1b, 1c, and 1f), were synthesized from 1-phenyl-2-phospholene 1-oxide 1a via 3-methyl-1-(3-nitrophenyl)-2-phospholene 1-oxide (1b). 1-(4-Bromophenyl)-2- phospholene 1e was prepared by Grignard coupling reaction of 1-chloro-3-methyl-2-phospholene 1-oxide with 4-bromophenylmagnesium bromide. 2,3-Dibromo-3-methyl-1-arylphospholane 1-oxides (2a-2e) were prepared by the addition reaction of bromine to the C=C double bond of 2-phospholenes 1a-1e. The substituent effect of the phenyl group of the 1-aryl-phospho lanes 2 on the observed anti-proliferative effect against U937 leukemia cell lines evaluated by MTT in vitro methods showed that 2,3-dibromo-3-methyl-1-(4-bromophenyl) phospholane (2e) was the most active among 2. These novel dibromophosphorus heterocyclic derivatives exhibit much higher anti-cancer activity than Gleevec (molecular targeting chemotherapeutic agent) against U937 cells.
- Yamada, Manabu,Asai, Kazuhide,Yamashita, Junko,Suyama, Takuya,Niimi, Taishi,Maddali, Kasthuraiah,Fujie, Michio,Nakamura, Satoki,Kimura, Motohiko,Tanaka, Yasutaka,Toda, Mitsuo,Yamashita, Mitsuji
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experimental part
p. 173 - 180
(2011/06/24)
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- 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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experimental part
p. 89 - 97
(2011/06/24)
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- Preparation and characterization of phospholanes and phospha sugars as novel anti-cancer agents
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Diastereo isomeric erythro and threo forms of 2, 3-epoxy-l- phenylphospholane 1-oxides were synthesized from threo and erythro forms of 2-bromo-3-hydroxy-l-phenylphospholane 1-oxides being prepared from l-phenyl-2-phospholene 1-oxide. Alternatively, the e
- Ito, Satoru,Yamashita, Mitsuji,Niimi, Taishi,Fujie, Michio,Reddy, Valium Krishna,Totsuka, Hirono,Haritha, Buchammagari,Maddali, Kasthuraiah,Nakamura, Satoki,Asai, Kazuhide,Suyama, Takuya,Yamashita, Junko,Iguchi, Yukiko,Yu, Gang,Oshikawa, Tatsuo
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experimental part
p. 23 - 30
(2010/03/03)
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