Synthesis and evaluation of novel phosphasugar anticancer agents

Yamaoka, Mayumi; Yamashita, Mitsuji; Yamada, Manabu; Fujie, Michio; Kiyofuji, Keita; Ozaki, Nobuhisa; Asai, Kazuhide; Niimi, Taishi; Suyama, Takuya; Yamashita, Junko; Sawada, Akiho; Makita, Reiko; Sugiyama, Masaki; Toda, Mitsuo; Nakamura, Satoki; Ohnishi, Kazunori

doi:10.1351/PAC-CON-11-10-09

Pure Appl. Chem., 2012, Vol. 84, No. 1, pp. 37-48

http://dx.doi.org/10.1351/PAC-CON-11-10-09

Published online 2011-12-27

Synthesis and evaluation of novel phosphasugar anticancer agents

Mayumi Yamaoka¹, Mitsuji Yamashita²*, Manabu Yamada², Michio Fujie^2,3, Keita Kiyofuji², Nobuhisa Ozaki², Kazuhide Asai¹, Taishi Niimi¹, Takuya Suyama¹, Junko Yamashita², Akiho Sawada⁴, Reiko Makita², Masaki Sugiyama², Mitsuo Toda⁴, Satoki Nakamura³ and Kazunori Ohnishi³

¹ Graduate School of Engineering, Shizuoka University, Hamamatsu 432-8561, Japan
² Graduate School of Science and Technology, Shizuoka University, Hamamatsu 432-8561, Japan
³ Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
⁴ Faculty of Engineering, Shizuoka University, Hamamatsu 432-8561, Japan

Abstract: Starting materials of phosphasugars, 1-phenyl-2-phospholene 1-oxides, were prepared from dienes and phenylphosphonous dichloride (dichlorophenylphosphine). Several substituted novel phosphasugars (3- or 4-halo-substituted)-1-phenyl-2-phospholene 1-oxides as well as 1-phenyl-2-phospholane 1-oxides were prepared from 2-phospholenes. The synthesized compounds were evaluated for their antitumor activities against the leukemia cell lines (U937 and K562) by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. 2,3,4-Tribromo-3-methyl-1-phenylphospholane 1-oxide showed superior antitumor activity against U937 and K562 cell lines in a comparative evaluation with Glivec. The analysis by flow cytometry implied that 2,3-dibromo-3-methyl-1-phenylphospholane 1‑oxide induced apoptosis to leukemia cell lines.