TY - JOUR
T1 - Synthesis, antiproliferative, and antiplatelet activities of oxime- and methyloxime-containing flavone and isoflavone derivatives
AU - Wang, Tai Chi
AU - Chen, I. Li
AU - Lu, Pei Jung
AU - Wong, Chui Hei
AU - Liao, Chang Hui
AU - Tsiao, Kuei Ching
AU - Chang, Ken Ming
AU - Chen, Yeh Long
AU - Tzeng, Cherng Chyi
N1 - Funding Information:
Financial support of this work by the National Science Council of the Republic of China is gratefully acknowledged. We also thank the National Cancer Institute (NCI, USA) for anticancer screenings and the National Center for High-Performance Computing for providing computer resources and chemical-database services.
PY - 2005/11/1
Y1 - 2005/11/1
N2 - 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 μM, respectively, against the growth of SKHep1; 0.9, 0.8, and 1.0 μM, respectively, against the growth of HeLa cells. Compound 18c is not only the most cytotoxic with a mean GI50 value of 0.08 μM 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 μM 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.
AB - 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 μM, respectively, against the growth of SKHep1; 0.9, 0.8, and 1.0 μM, respectively, against the growth of HeLa cells. Compound 18c is not only the most cytotoxic with a mean GI50 value of 0.08 μM 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 μM 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.
UR - http://www.scopus.com/inward/record.url?scp=25844486965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25844486965&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2005.06.004
DO - 10.1016/j.bmc.2005.06.004
M3 - Article
C2 - 15990314
AN - SCOPUS:25844486965
SN - 0968-0896
VL - 13
SP - 6045
EP - 6053
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 21
ER -