Inhibitory Effects of Bis(2-aminohexyl)disulfide and Its Analogues on Polymorphonuclear Leukocyte Functions in Vitro

Yasuhiro Kohama, Masaru Okabe, Tsujikawa Kazutake, Tetsuyuki Teramoto, Norihito Murayama, Tsutomu Mimura, Takuzo Ohtani, Takefumi Matsukura, Yuzo Kayamori, Yoshiaki Katayama

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Abstract

Water soluble analogues of the anti-inflammatory compound, bis(2-aminopropyl)disulfide dihydrochloride (compd. I) with a butyl (II), phenyl (III), benzyl (IV) or pyrrolidinyl group (V) instead of the methyl group were synthesized, and their effects on the functions of cells related to inflammation were studied in vitro. Compounds II, III and IV showed much higher inhibitory activity than compd. I on formyl Met-Leu-Phe (FMLP)-induced O - 2 -generation of polymorphonuclear leukocytes (PMNs) and platelet aggregation. Compound II showed the strongest activity among the compounds (IC50 values: 2.6 /im).The inhibition of O2-generation of PMNs by compd. II was the most effective when FMLP was used as a stimulant rather than when phorbol myristate acetate, A-23187 and opsonized zymosan were used. However, compd. II was not an O 2-scavenger. Compounds II, III and IV significantly inhibited a series of activation processes in PMNs, chemotaxis, phagocytosis and lysosomal enzyme release at doses ranging from 10 to 100 /im. Under these doses, compds II, III and IV did not affect the histamine release from mast cells or the hemolysis of erythrocytes. These results strongly suggest that the anti-inflammatory action caused by compd. II and its analogues was at least partly due to inhibition of several functions of PMNs and platelets.

Original languageEnglish
Pages (from-to)414-418
Number of pages5
JournalChemical and Pharmaceutical Bulletin
Volume40
Issue number2
DOIs
Publication statusPublished - Jan 1 1992

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methionyl-leucyl-phenylalanine
Platelets
Neutrophils
Anti-Inflammatory Agents
Zymosan
Histamine Release
Calcimycin
Tetradecanoylphorbol Acetate
Chemotaxis
Hemolysis
Platelet Aggregation
Phagocytosis
Mast Cells
Disulfides
Histamine
Inhibitory Concentration 50
Blood Platelets
Agglomeration
Erythrocytes
Chemical activation

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

Cite this

Inhibitory Effects of Bis(2-aminohexyl)disulfide and Its Analogues on Polymorphonuclear Leukocyte Functions in Vitro. / Kohama, Yasuhiro; Okabe, Masaru; Kazutake, Tsujikawa; Teramoto, Tetsuyuki; Murayama, Norihito; Mimura, Tsutomu; Ohtani, Takuzo; Matsukura, Takefumi; Kayamori, Yuzo; Katayama, Yoshiaki.

In: Chemical and Pharmaceutical Bulletin, Vol. 40, No. 2, 01.01.1992, p. 414-418.

Research output: Contribution to journalArticle

Kohama, Y, Okabe, M, Kazutake, T, Teramoto, T, Murayama, N, Mimura, T, Ohtani, T, Matsukura, T, Kayamori, Y & Katayama, Y 1992, 'Inhibitory Effects of Bis(2-aminohexyl)disulfide and Its Analogues on Polymorphonuclear Leukocyte Functions in Vitro', Chemical and Pharmaceutical Bulletin, vol. 40, no. 2, pp. 414-418. https://doi.org/10.1248/cpb.40.414
Kohama, Yasuhiro ; Okabe, Masaru ; Kazutake, Tsujikawa ; Teramoto, Tetsuyuki ; Murayama, Norihito ; Mimura, Tsutomu ; Ohtani, Takuzo ; Matsukura, Takefumi ; Kayamori, Yuzo ; Katayama, Yoshiaki. / Inhibitory Effects of Bis(2-aminohexyl)disulfide and Its Analogues on Polymorphonuclear Leukocyte Functions in Vitro. In: Chemical and Pharmaceutical Bulletin. 1992 ; Vol. 40, No. 2. pp. 414-418.
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