Synthesis and antiproliferative evaluation of piperazine-1-carbothiohydrazide derivatives of indolin-2-one.

Abstract

By varying the substituents (R(1)) at the indolin-2-one scaffold, a series of indolin-2-one derivatives bearing 4-phenylpiperazine-1-carbothiohydrazide moiety at the C3-position were synthesized and evaluated for their antiproliferative activity against three human cancer cell lines. We further selected the 5-chloroindolin-2-one moiety for the extension to another series of compounds by varying the substituents (R(2)) at the phenyl group connected with the piperazine ring. Among all the compounds synthesized, 6d and 6l were most potent with IC50 values of 3.59 and 5.58 μM, respectively against A549 lung cancer cells, while 5f and 6l possessed IC50 values of 3.49 and 4.57 μM, respectively against HCT-116 colon cancer cells which were comparable to that of Sunitinib, an indolin-2-one derivative in cancer therapy.

• Authors: Hui-Hui Lin, Wei-Yao Wu, Sheng-Li Cao, Ji Liao, Li Ma, Man Gao, Zhong-Feng Li, Xingzhi Xu
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 23 Issue 11 Pg. 3304-7 (Jun 01 2013) ISSN: 1464-3405 [Electronic] England
• PMID: 23602441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Hydrazines
• Indoles
• Piperazines
• indolin-2-one
• Piperazine
• hydrazine

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Screening Assays, Antitumor
• HCT116 Cells
• Humans
• Hydrazines (chemical synthesis, chemistry)
• Indoles (chemistry)
• Piperazine
• Piperazines (chemistry)
• Structure-Activity Relationship