Synthesis, antiproliferative, and antiplatelet activities of oxime- and methyloxime-containing flavone and isoflavone derivatives

Tai Chi Wang, I. Li Chen, Pei-Jung Lu, Chui Hei Wong, Chang Hui Liao, Kuei Ching Tsiao, Ken Ming Chang, Yeh Long Chen, Cherng Chyi Tzeng

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Abstract

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.

Original languageEnglish
Pages (from-to)6045-6053
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume13
Issue number21
DOIs
Publication statusPublished - 2005 Nov 1

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flavone
Isoflavones
Oximes
Cells
Growth
Tumor Cell Line
Derivatives
Tumors
G2 Phase
Platelet Aggregation Inhibitors
Taiwan
HeLa Cells
Cell Division
Hepatocellular Carcinoma
Squamous Cell Carcinoma
Assays
Apoptosis
Carcinoma

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Wang, Tai Chi ; Chen, I. Li ; Lu, Pei-Jung ; Wong, Chui Hei ; Liao, Chang Hui ; Tsiao, Kuei Ching ; Chang, Ken Ming ; Chen, Yeh Long ; Tzeng, Cherng Chyi. / Synthesis, antiproliferative, and antiplatelet activities of oxime- and methyloxime-containing flavone and isoflavone derivatives. In: Bioorganic and Medicinal Chemistry. 2005 ; Vol. 13, No. 21. pp. 6045-6053.
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abstract = "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.",
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Synthesis, antiproliferative, and antiplatelet activities of oxime- and methyloxime-containing flavone and isoflavone derivatives. / Wang, Tai Chi; Chen, I. Li; Lu, Pei-Jung; Wong, Chui Hei; Liao, Chang Hui; Tsiao, Kuei Ching; Chang, Ken Ming; Chen, Yeh Long; Tzeng, Cherng Chyi.

In: Bioorganic and Medicinal Chemistry, Vol. 13, No. 21, 01.11.2005, p. 6045-6053.

Research output: Contribution to journalArticle

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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

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