Synthesis, and cytotoxic and antiplatelet activities of oxime- and methyloxime-containing flavone, isoflavone, and xanthone derivatives.
A series of oxime- and methyloxime-containing flavone, isoflavone, and xanthone derivatives (1-12) were synthesized (Scheme) and evaluated for their cytotoxic (Table 1) and antiplatelet activities (Table 2). The in vitro anticancer assay indicated that the cytotoxicity of structurally related compounds decreases in the order isoflavones (7a-7c) > flavones (8a-8c) > xanthones (9a-9c), electron-releasing substituents (R) on the Ph ring being favorable (mean GI50 values of 2.84, 12.3, and 20.9 microM for 7c, 8c, and 9c, resp.). The inhibition of platelet aggregation induced by arachidonic acid (AA) similarly decreased from the isoflavone 1 (IC50 = 2.97 microM) to the flavone 2 (7.70 microM) to the xanthone 3 (inactive). Thereby, compound 1 seems to be a promising lead, since it was not only the most-potent aggregation inhibitor (IC50 = 2.97 microM), but was also found to be noncytotoxic at a concentration of 100 microM.
Wang
Tai-Chi
TC
Department of Pharmacy, Tajen Institute of Technology, Pingtung 907, Taiwan, Republic of China. tcwang@ccsun.tajen.edu.tw
Chen
I-Li
IL
Lu
Chai-Ming
CM
Kuo
Daih-Huang
DH
Liao
Chang-Hui
CH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D047309:Flavones / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D044004:Xanthones / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D047309:Flavones; D007529:Isoflavones; D010975:Platelet Aggregation Inhibitors; D044004:Xanthones