Biological evaluation of sulfone derivatives as anti-inflammatory and tumor cells growth inhibitory agents.
A variety of sulfone derivatives including three dimethyl arylsulfonyl malonates (1-3), two bis-(arylethenesulfonyl)-vinyl benzenes (4 and 5) and a sulfone triazole (6) were evaluated for their anti-inflammatory as well as tumor cells growth inhibitory activities in vitro. The sulfone derivatives 1, 2, 3 and 6 significantly and dose-dependently inhibited the production of inflammatory mediators such as nitric oxide (NO), and cytokines (tumor necrosis factor (TNF)-alpha and interleukin (IL)-12), in lipopolysaccharide (LPS) and interferon (IFN)-gamma activated murine peritoneal macrophages, without displaying cytotoxicity. The inhibitory mechanism is found through reducing iNOS protein expression. In addition, the derivatives 1-3 significantly arrest mitogen-stimulated spleen cells in G0/G1 stage, whereas compounds 4-6 blocked the same in the G2/M phase. Furthermore, the sulfone derivatives 3 and 6 showed dramatically reduction in the ratio of IFN-gamma to IL-4 production from mitogen-stimulated spleen cells. On the other hand, the novel compounds exhibited interesting cytotoxic activities against a panel of cell lines, particularly, 20 muM of compound 3 showed 50% cytotoxic effect on human hepatoma cell line, but has no effect on normal human peripheral blood mononuclear cells. In conclusion, compound 3 showed interesting anti-inflammatory and tumor cells growth inhibitory functions.
Fang
Shih-Hua
SH
Department of Microbiology, School of Medicine, China Medical University, Taichung 404, Taiwan, ROC.
Padmavathi
V
V
Rao
Yerra Koteswara
YK
Venkata Subbaiah
D R C
DR
Thriveni
P
P
Geethangili
Madamanchi
M
Padmaja
A
A
Tzeng
Yew-Min
YM
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008314:Malonates / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013450:Sulfones / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D008314:Malonates; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II