Synthesis, antiproliferative, and antiplatelet activities of oxime- and methyloxime-containing flavone and isoflavone derivatives.
Certain oxime- and methyloxime-containing flavone and isoflavone derivatives were synthesized and evaluated for their antiproliferative activity against three solid cancer cells, human cervical epithelioid carcinoma (HeLa), hepatocellular carcinoma (SKHep1), and oral squamous cell carcinoma (SAS), which are commonly seen in Asian countries, including Taiwan. Selective compounds were also evaluated in the full panel of 60 human tumor cell lines and their mean GI50 values were obtained. The preliminary assays indicated flavone-6-yl derivatives are the most cytotoxic while isoflavone-7-yl derivatives are the best antiplatelet agents. Among them, (E)-6-(2-methoxyiminopropoxy)-2-phenyl-4H-1-benzopyran-4-one (14), (Z)-6-(2-hydroxyimino-2-phenylethoxy)-2-phenyl-4H-1-benzopyran-4-one (18a), and (Z)-6-[2-hydroxyimino-2-(4-methoxyphenyl)ethoxy]-2-phenyl-4H-1-benzopyran-4-one (18c) are three of the best antiproliferative agents with GI50 values of 0.8, 0.7, and 0.8 microM, respectively, against the growth of SKHep1; 0.9, 0.8, and 1.0 microM, respectively, against the growth of HeLa cells. Compound 18c is not only the most cytotoxic with a mean GI50 value of 0.08 microM against the full panel of 60 human tumor cell lines but also the only flavone derivative that exhibited a GI50 value of less than 1 microM against the growth of SAS. Flow cytometric analyses revealed that growth inhibition by 18c was due to accumulation in G2/M phase arrest and followed by apoptosis.
Department of Pharmacy, Tajen Institute of Technology, Pingtung 907, Taiwan.
Tai-Chi
TC
Wang
I-Li
IL
Chen
Pei-Jung
PJ
Lu
Chui-Hei
CH
Wong
Chang-Hui
CH
Liao
Kuei-Ching
KC
Tsiao
Ken-Ming
KM
Chang
Yeh-Long
YL
Chen
Cherng-Chyi
CC
Tzeng
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047309:Flavones; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008745:Methylation; D015394:Molecular Structure; D009369:Neoplasms / Q000473:pathology*; D010091:Oximes / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship
D047309:Flavones; D005419:Flavonoids; D007529:Isoflavones; D010091:Oximes; C043562:flavone