Synthesis and cytotoxicity of 9-alkoxy-1,5-dichloroanthracene derivatives in murine and human cultured tumor cells

Hsu-Shan Huang, Jeng-Fong Chiou, Hui-Fen Chiu, Rong-Fu Chen, Yu-Liang Lai

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

9-Alkoxy-1,5-dichloroanthracenes were successfully prepared. Their cytotoxicity was evaluated in vitro on rat glioma C6 cell lines and human hepatoma G2 cell lines, respectively. Alkylation of 1,5-dichloro-9(10H)-anthracenone with either the appropriate alcohols or alkyl chlorides in the presence of sulfuric acid or sodium hydride, respectively, furnished this structural class of anthracenes. Contrary to mitoxantrone, cytotoxic properties were observed as documented by the reactivity of the novel compounds and potent in vitro activity against C6 cells and hep G2 cells over a wide range of structural variants. Among these compounds, 5c, 5h, 5l and 5n are potent cytotoxins. They inhibit C6 cell growth in culture, indicated by using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt (XTT) colorimetric assay. By using this assay it was also shown that 5c, 5d and 5l possess potent cytotoxicity on hep G2 cells. The most active compound displaying in vitro cytotoxicity was the 9-butoxy derivative 5h with IC50 values 0.02 microM against C6 cells, as compared with mitoxantrone with IC50 values 0.07 microM. The most active compound displaying in vitro cytotoxicity against hep G2 cells was 5c with IC50 values 1.7 microM (mitoxantrone: 0.8 microM). Structure-activity relationships (SAR) of these compounds with respect to the nature of the alkoxy substitution in the 9 position are discussed for both cell lines.

Original languageEnglish
Pages (from-to)33-8
Number of pages6
JournalArchiv der Pharmazie
Volume335
Issue number1
Publication statusPublished - Jan 2002

Fingerprint

Cultured Tumor Cells
Mitoxantrone
Hep G2 Cells
Inhibitory Concentration 50
Cell Line
Anthracenes
Cytotoxins
Alkylation
Structure-Activity Relationship
Glioma
Chlorides
Hepatocellular Carcinoma
Salts
Sodium
Alcohols
alkoxyl radical
In Vitro Techniques
Growth

Keywords

  • Animals
  • Anthracenes
  • Antineoplastic Agents
  • Cell Division
  • Humans
  • Hydrocarbons, Chlorinated
  • Mice
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Synthesis and cytotoxicity of 9-alkoxy-1,5-dichloroanthracene derivatives in murine and human cultured tumor cells. / Huang, Hsu-Shan; Chiou, Jeng-Fong; Chiu, Hui-Fen; Chen, Rong-Fu; Lai, Yu-Liang.

In: Archiv der Pharmazie, Vol. 335, No. 1, 01.2002, p. 33-8.

Research output: Contribution to journalArticle

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abstract = "9-Alkoxy-1,5-dichloroanthracenes were successfully prepared. Their cytotoxicity was evaluated in vitro on rat glioma C6 cell lines and human hepatoma G2 cell lines, respectively. Alkylation of 1,5-dichloro-9(10H)-anthracenone with either the appropriate alcohols or alkyl chlorides in the presence of sulfuric acid or sodium hydride, respectively, furnished this structural class of anthracenes. Contrary to mitoxantrone, cytotoxic properties were observed as documented by the reactivity of the novel compounds and potent in vitro activity against C6 cells and hep G2 cells over a wide range of structural variants. Among these compounds, 5c, 5h, 5l and 5n are potent cytotoxins. They inhibit C6 cell growth in culture, indicated by using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt (XTT) colorimetric assay. By using this assay it was also shown that 5c, 5d and 5l possess potent cytotoxicity on hep G2 cells. The most active compound displaying in vitro cytotoxicity was the 9-butoxy derivative 5h with IC50 values 0.02 microM against C6 cells, as compared with mitoxantrone with IC50 values 0.07 microM. The most active compound displaying in vitro cytotoxicity against hep G2 cells was 5c with IC50 values 1.7 microM (mitoxantrone: 0.8 microM). Structure-activity relationships (SAR) of these compounds with respect to the nature of the alkoxy substitution in the 9 position are discussed for both cell lines.",
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T1 - Synthesis and cytotoxicity of 9-alkoxy-1,5-dichloroanthracene derivatives in murine and human cultured tumor cells

AU - Huang, Hsu-Shan

AU - Chiou, Jeng-Fong

AU - Chiu, Hui-Fen

AU - Chen, Rong-Fu

AU - Lai, Yu-Liang

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N2 - 9-Alkoxy-1,5-dichloroanthracenes were successfully prepared. Their cytotoxicity was evaluated in vitro on rat glioma C6 cell lines and human hepatoma G2 cell lines, respectively. Alkylation of 1,5-dichloro-9(10H)-anthracenone with either the appropriate alcohols or alkyl chlorides in the presence of sulfuric acid or sodium hydride, respectively, furnished this structural class of anthracenes. Contrary to mitoxantrone, cytotoxic properties were observed as documented by the reactivity of the novel compounds and potent in vitro activity against C6 cells and hep G2 cells over a wide range of structural variants. Among these compounds, 5c, 5h, 5l and 5n are potent cytotoxins. They inhibit C6 cell growth in culture, indicated by using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt (XTT) colorimetric assay. By using this assay it was also shown that 5c, 5d and 5l possess potent cytotoxicity on hep G2 cells. The most active compound displaying in vitro cytotoxicity was the 9-butoxy derivative 5h with IC50 values 0.02 microM against C6 cells, as compared with mitoxantrone with IC50 values 0.07 microM. The most active compound displaying in vitro cytotoxicity against hep G2 cells was 5c with IC50 values 1.7 microM (mitoxantrone: 0.8 microM). Structure-activity relationships (SAR) of these compounds with respect to the nature of the alkoxy substitution in the 9 position are discussed for both cell lines.

AB - 9-Alkoxy-1,5-dichloroanthracenes were successfully prepared. Their cytotoxicity was evaluated in vitro on rat glioma C6 cell lines and human hepatoma G2 cell lines, respectively. Alkylation of 1,5-dichloro-9(10H)-anthracenone with either the appropriate alcohols or alkyl chlorides in the presence of sulfuric acid or sodium hydride, respectively, furnished this structural class of anthracenes. Contrary to mitoxantrone, cytotoxic properties were observed as documented by the reactivity of the novel compounds and potent in vitro activity against C6 cells and hep G2 cells over a wide range of structural variants. Among these compounds, 5c, 5h, 5l and 5n are potent cytotoxins. They inhibit C6 cell growth in culture, indicated by using 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide sodium salt (XTT) colorimetric assay. By using this assay it was also shown that 5c, 5d and 5l possess potent cytotoxicity on hep G2 cells. The most active compound displaying in vitro cytotoxicity was the 9-butoxy derivative 5h with IC50 values 0.02 microM against C6 cells, as compared with mitoxantrone with IC50 values 0.07 microM. The most active compound displaying in vitro cytotoxicity against hep G2 cells was 5c with IC50 values 1.7 microM (mitoxantrone: 0.8 microM). Structure-activity relationships (SAR) of these compounds with respect to the nature of the alkoxy substitution in the 9 position are discussed for both cell lines.

KW - Animals

KW - Anthracenes

KW - Antineoplastic Agents

KW - Cell Division

KW - Humans

KW - Hydrocarbons, Chlorinated

KW - Mice

KW - Structure-Activity Relationship

KW - Tumor Cells, Cultured

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - Article

C2 - 11933678

VL - 335

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JO - Archiv der Pharmazie

JF - Archiv der Pharmazie

SN - 0365-6233

IS - 1

ER -