Abstract

Background: Cantharidin isolated from the blister beetle is used as a traditional Chinese medicine. The anticancer activity of thiadizolyl and some known N-substituted thiazolyl of cantharidin has been reported. We obtained a novel type of cantharidinimides for testing their cytotoxicity in human carcinoma cell lines. The structural modification of cantharidin to cantharidinimide might lead to the discovery of a novel class of antitumor compounds. Methods: We synthesized more than 34 cantharidinimide derivatives from heating the cantharidin (compound 1) to ca. 200°Cin toluene and triethylamine along with primary amine, aniline derivatives, and aminopyridines, respectively. These imide derivatives contain aryl, pyridyl, azolyl, thiadiazolyl, diaminophenyl, aminosulfanyl, sulfamethoxazolyl, or sulfadiazine cantharidinimides (compounds 2-34). All of these synthetic compounds were tested for their capability to suppress growth of the human carcinoma cell lines such as HepG2, HL-60, 59T, HONE-1, DLD-1, SCM-1 NUGC, and Hep3B cells. Results: The 3-(4, 5-dimethylthiazol-2-yl)2, 5-diphenyltetrazolium bromide (MTT) viability assay was used to evaluate the cytotoxic effect of newly synthesized cantharidinimides against the previously mentioned carcinoma cell lines. The current results indicate that compounds 2, 3, 4, 6, 8, 11, 12, 13, 14, 15, 17, 29, 30, and 31 were somehow effective and some of them were more potent than the parent compound cantharidin. Compounds 4, 13, 14, and 15, which were thiazol- and thiadiazol-containing cantharidinimides, caused cytotoxic effects on 59T, SCM-1, HONE-1, Hep3B, and NUGC human carcinoma cell lines. Compounds 11 and 16 with a planar side chain had medium cytotoxicity on hepatoma cell lines. Compounds 6 and 8 were bromine-containing aromatic cantharidinimide that produced significant cytotoxic effects on HONE-I and NUGC in high concentrations, but only compound 6 inhibited the growth of 59T and SCM-1 cell lines. Conclusions: The current results indicate that the cytotoxic effects on several cancer cells were produced by many different structural domains of the cantharidinimide compounds. The current in vitro results suggest that decreasing electron negativity on the substituent-donating group might increase their cytotoxicity to cancer cells.

Original languageEnglish
Pages (from-to)280-283
Number of pages4
JournalJournal of Experimental and Clinical Medicine(Taiwan)
Volume4
Issue number5
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Cantharidin
Cell Line
Carcinoma
Neoplasms
Aminopyridines
Imides
Sulfadiazine
Bromine
Beetles
Chinese Traditional Medicine
Toluene
Blister
Growth
Heating
Amines
Hepatocellular Carcinoma
Electrons

Keywords

  • Blister beetle
  • Cantharidin
  • Cantharidinimide
  • Cytotoxicity
  • Human cancer cells
  • Mylabris caraganae

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Synthesis and Evaluation of Cantharidinimides on Human Cancer Cells. / Tseng, Ing Jy; Sheu, Shiow Yunn; Lin, Pen Yuan; Lee, Jen Ai; Ou, Keng Liang; Lee, Lin Wen.

In: Journal of Experimental and Clinical Medicine(Taiwan), Vol. 4, No. 5, 10.2012, p. 280-283.

Research output: Contribution to journalArticle

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abstract = "Background: Cantharidin isolated from the blister beetle is used as a traditional Chinese medicine. The anticancer activity of thiadizolyl and some known N-substituted thiazolyl of cantharidin has been reported. We obtained a novel type of cantharidinimides for testing their cytotoxicity in human carcinoma cell lines. The structural modification of cantharidin to cantharidinimide might lead to the discovery of a novel class of antitumor compounds. Methods: We synthesized more than 34 cantharidinimide derivatives from heating the cantharidin (compound 1) to ca. 200°Cin toluene and triethylamine along with primary amine, aniline derivatives, and aminopyridines, respectively. These imide derivatives contain aryl, pyridyl, azolyl, thiadiazolyl, diaminophenyl, aminosulfanyl, sulfamethoxazolyl, or sulfadiazine cantharidinimides (compounds 2-34). All of these synthetic compounds were tested for their capability to suppress growth of the human carcinoma cell lines such as HepG2, HL-60, 59T, HONE-1, DLD-1, SCM-1 NUGC, and Hep3B cells. Results: The 3-(4, 5-dimethylthiazol-2-yl)2, 5-diphenyltetrazolium bromide (MTT) viability assay was used to evaluate the cytotoxic effect of newly synthesized cantharidinimides against the previously mentioned carcinoma cell lines. The current results indicate that compounds 2, 3, 4, 6, 8, 11, 12, 13, 14, 15, 17, 29, 30, and 31 were somehow effective and some of them were more potent than the parent compound cantharidin. Compounds 4, 13, 14, and 15, which were thiazol- and thiadiazol-containing cantharidinimides, caused cytotoxic effects on 59T, SCM-1, HONE-1, Hep3B, and NUGC human carcinoma cell lines. Compounds 11 and 16 with a planar side chain had medium cytotoxicity on hepatoma cell lines. Compounds 6 and 8 were bromine-containing aromatic cantharidinimide that produced significant cytotoxic effects on HONE-I and NUGC in high concentrations, but only compound 6 inhibited the growth of 59T and SCM-1 cell lines. Conclusions: The current results indicate that the cytotoxic effects on several cancer cells were produced by many different structural domains of the cantharidinimide compounds. The current in vitro results suggest that decreasing electron negativity on the substituent-donating group might increase their cytotoxicity to cancer cells.",
keywords = "Blister beetle, Cantharidin, Cantharidinimide, Cytotoxicity, Human cancer cells, Mylabris caraganae",
author = "Tseng, {Ing Jy} and Sheu, {Shiow Yunn} and Lin, {Pen Yuan} and Lee, {Jen Ai} and Ou, {Keng Liang} and Lee, {Lin Wen}",
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T1 - Synthesis and Evaluation of Cantharidinimides on Human Cancer Cells

AU - Tseng, Ing Jy

AU - Sheu, Shiow Yunn

AU - Lin, Pen Yuan

AU - Lee, Jen Ai

AU - Ou, Keng Liang

AU - Lee, Lin Wen

PY - 2012/10

Y1 - 2012/10

N2 - Background: Cantharidin isolated from the blister beetle is used as a traditional Chinese medicine. The anticancer activity of thiadizolyl and some known N-substituted thiazolyl of cantharidin has been reported. We obtained a novel type of cantharidinimides for testing their cytotoxicity in human carcinoma cell lines. The structural modification of cantharidin to cantharidinimide might lead to the discovery of a novel class of antitumor compounds. Methods: We synthesized more than 34 cantharidinimide derivatives from heating the cantharidin (compound 1) to ca. 200°Cin toluene and triethylamine along with primary amine, aniline derivatives, and aminopyridines, respectively. These imide derivatives contain aryl, pyridyl, azolyl, thiadiazolyl, diaminophenyl, aminosulfanyl, sulfamethoxazolyl, or sulfadiazine cantharidinimides (compounds 2-34). All of these synthetic compounds were tested for their capability to suppress growth of the human carcinoma cell lines such as HepG2, HL-60, 59T, HONE-1, DLD-1, SCM-1 NUGC, and Hep3B cells. Results: The 3-(4, 5-dimethylthiazol-2-yl)2, 5-diphenyltetrazolium bromide (MTT) viability assay was used to evaluate the cytotoxic effect of newly synthesized cantharidinimides against the previously mentioned carcinoma cell lines. The current results indicate that compounds 2, 3, 4, 6, 8, 11, 12, 13, 14, 15, 17, 29, 30, and 31 were somehow effective and some of them were more potent than the parent compound cantharidin. Compounds 4, 13, 14, and 15, which were thiazol- and thiadiazol-containing cantharidinimides, caused cytotoxic effects on 59T, SCM-1, HONE-1, Hep3B, and NUGC human carcinoma cell lines. Compounds 11 and 16 with a planar side chain had medium cytotoxicity on hepatoma cell lines. Compounds 6 and 8 were bromine-containing aromatic cantharidinimide that produced significant cytotoxic effects on HONE-I and NUGC in high concentrations, but only compound 6 inhibited the growth of 59T and SCM-1 cell lines. Conclusions: The current results indicate that the cytotoxic effects on several cancer cells were produced by many different structural domains of the cantharidinimide compounds. The current in vitro results suggest that decreasing electron negativity on the substituent-donating group might increase their cytotoxicity to cancer cells.

AB - Background: Cantharidin isolated from the blister beetle is used as a traditional Chinese medicine. The anticancer activity of thiadizolyl and some known N-substituted thiazolyl of cantharidin has been reported. We obtained a novel type of cantharidinimides for testing their cytotoxicity in human carcinoma cell lines. The structural modification of cantharidin to cantharidinimide might lead to the discovery of a novel class of antitumor compounds. Methods: We synthesized more than 34 cantharidinimide derivatives from heating the cantharidin (compound 1) to ca. 200°Cin toluene and triethylamine along with primary amine, aniline derivatives, and aminopyridines, respectively. These imide derivatives contain aryl, pyridyl, azolyl, thiadiazolyl, diaminophenyl, aminosulfanyl, sulfamethoxazolyl, or sulfadiazine cantharidinimides (compounds 2-34). All of these synthetic compounds were tested for their capability to suppress growth of the human carcinoma cell lines such as HepG2, HL-60, 59T, HONE-1, DLD-1, SCM-1 NUGC, and Hep3B cells. Results: The 3-(4, 5-dimethylthiazol-2-yl)2, 5-diphenyltetrazolium bromide (MTT) viability assay was used to evaluate the cytotoxic effect of newly synthesized cantharidinimides against the previously mentioned carcinoma cell lines. The current results indicate that compounds 2, 3, 4, 6, 8, 11, 12, 13, 14, 15, 17, 29, 30, and 31 were somehow effective and some of them were more potent than the parent compound cantharidin. Compounds 4, 13, 14, and 15, which were thiazol- and thiadiazol-containing cantharidinimides, caused cytotoxic effects on 59T, SCM-1, HONE-1, Hep3B, and NUGC human carcinoma cell lines. Compounds 11 and 16 with a planar side chain had medium cytotoxicity on hepatoma cell lines. Compounds 6 and 8 were bromine-containing aromatic cantharidinimide that produced significant cytotoxic effects on HONE-I and NUGC in high concentrations, but only compound 6 inhibited the growth of 59T and SCM-1 cell lines. Conclusions: The current results indicate that the cytotoxic effects on several cancer cells were produced by many different structural domains of the cantharidinimide compounds. The current in vitro results suggest that decreasing electron negativity on the substituent-donating group might increase their cytotoxicity to cancer cells.

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KW - Cantharidin

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KW - Cytotoxicity

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KW - Mylabris caraganae

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