Cytotoxic activity of azulenes against human oral tumor cell lines
Wakabayashi, H.; Hashiba, K.; Yokoyama, K.; Hashimoto, K.; Kikuchi, H.; Nishikawa, H.; Kurihara, T.; Satoh, K.; Shioda, S.; Saito, S.; Kusano, S.; Nakashima, H.; Motohashi, N.; Sakagami, H.
Anticancer Research 23(6c): 4747-4755
2003
ISSN/ISBN: 0250-7005 PMID: 14981922 Document Number: 555626
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].