Cytotoxic activity of azulenes against human oral tumor cell lines.
We investigated 27 azulene derivatives for their relative cytotoxicity against three human normal cells and three human oral tumor cell lines. 2-Acetylaminoazulene [4], diethyl 2-chlorozulene-1,3-dicarboxylate [9] and methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24] showed higher tumor-specific cytotoxicity than azulene [1] and guaiazulene [2]. Four 1- and 3-halogenated compounds showed lower tumor specificity. The tumor-specific cytotoxic activity seems not to be related to the position of functional groups. All compounds showed no anti-HIV activity. Methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24] induced apoptotic cell death (characterized by internucleosomal DNA fragmentation and caspase 3 activation) in HL-60 cells. ESR spectroscopy showed that methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24] did not produce radical and less efficiently scavenged O2- (generated by HX-XOD reaction) and NO (generated from NOC-7). These data suggest that a radical-mediated oxidation mechanism may not be involved in the apoptosis induction by methyl 7-isopropyl-2-methoxyazulene-1-carboxylate [24].
Wakabayashi
Hidetsugu
H
Faculty of Science, Josai University, Sakado, Saitama, 350-0295, Japan. hwaka@josai.ac.jp
Hashiba
Kana
K
Yokoyama
Keiko
K
Hashimoto
Ken
K
Kikuchi
Hirotaka
H
Nishikawa
Hirofumi
H
Kurihara
Teruo
T
Satoh
Kazue
K
Shioda
Seiji
S
Saito
Susumu
S
Kusano
Shuichi
S
Nakashima
Hideki
H
Motohashi
Noboru
N
Sakagami
Hiroshi
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D052176:Azulenes; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D003508:Cycloheptanes / Q000737:chemistry* / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D015394:Molecular Structure; D009062:Mouth Neoplasms; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052176:Azulenes; D003508:Cycloheptanes; C005525:azulene