Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives

Gao Xiang Zhu, Pi Le Cheng, Masuo Goto, Na Zhang, Susan L. Morris-Natschke, Kan Yen Hsieh, Guan Zhou Yang, Qian Ru Yang, Ying Qian Liu, Hai Le Chen, Xiao Shuai Zhang, Kuo Hsiung Lee

Research output: Contribution to journalArticle

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Abstract

In an effort to discover potent camptothecin-derived antitumor agents, novel camptothecin analogues with sulfonylpiperazinyl motifs at position-7 were designed and synthesized. They were evaluated for in vitro cytotoxicity with the sulforhodamine-B (SRB) method in five types of human tumor cell lines, A-549, MDA-MB-231, KB, KB-VIN and MCF-7. With IC50 values in the low μM to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan. Furthermore, compounds 12l (IC50, 1.2 nM) and 12k (IC50, 20.2 nM) displayed the highest cytotoxicity against the multidrug-resistant (MDR) KB-VIN cell line and merit further development as preclinical drug candidates for treating cancer, including MDR phenotype. Our study suggested that integration of sulfonylpiperazinyl motifs into position-7 of camptothecin is an effective strategy for discovering new potent cytotoxic camptothecin derivatives.

LanguageEnglish (US)
Pages1750-1753
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number8
DOIs
StatePublished - 2017

Fingerprint

Camptothecin
Cytotoxicity
Inhibitory Concentration 50
Derivatives
irinotecan
lissamine rhodamine B
Cells
Topotecan
KB Cells
Tumor Cell Line
Antineoplastic Agents
Tumors
Phenotype
Cell Line
Pharmaceutical Preparations
Neoplasms

Keywords

  • Camptothecin
  • Cytotoxic activity
  • Sulfonylpiperazine
  • Synthesis

ASJC Scopus subject areas

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

Cite this

Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives. / Zhu, Gao Xiang; Cheng, Pi Le; Goto, Masuo; Zhang, Na; Morris-Natschke, Susan L.; Hsieh, Kan Yen; Yang, Guan Zhou; Yang, Qian Ru; Liu, Ying Qian; Chen, Hai Le; Zhang, Xiao Shuai; Lee, Kuo Hsiung.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 8, 2017, p. 1750-1753.

Research output: Contribution to journalArticle

Zhu, Gao Xiang ; Cheng, Pi Le ; Goto, Masuo ; Zhang, Na ; Morris-Natschke, Susan L. ; Hsieh, Kan Yen ; Yang, Guan Zhou ; Yang, Qian Ru ; Liu, Ying Qian ; Chen, Hai Le ; Zhang, Xiao Shuai ; Lee, Kuo Hsiung. / Design, synthesis and potent cytotoxic activity of novel 7-(N-[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives. In: Bioorganic and Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 8. pp. 1750-1753.
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AU - Yang, Guan Zhou

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AU - Chen, Hai Le

AU - Zhang, Xiao Shuai

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