Synthesis and in vitro cytotoxicity of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives.
A series of 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4-pyrimidinone derivatives were synthesized and their anticancer cytotoxicity were evaluated in in vitro assay. It was found that the bulky aryl functionality in the 5-position of the 2-cyanoimino-4-imidazolidinone compounds was essential for the cytotoxicity of these heterocyclic compounds. Some of the derivatives exhibited modest cytotoxicity against a variety of cancer cell lines. One of the derivatives, [1-[6-(4-chlorophenoxy)hexyl]-5-oxo-4-phenyl-3-(4-pyridyl)tetrahydro-1H-2-imidazolyliden]aminomethanenitrile (Compound 11), exhibited the most potent cytotoxic activity with IC(50) in the nanomolar range. The cytotoxicity of these derivatives was selection with no apparent toxic effect toward normal fibroblasts.
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taipei 114, Taiwan. jhchen@nhri.org.tw
Jyh-Haur
JH
Chern
Kak-Shan
KS
Shia
Chung-Ming
CM
Chang
Chung-Chi
CC
Lee
Yen-Chun
YC
Lee
Chia-Liang
CL
Tai
Ying-Ting
YT
Lin
Chih-Shiang
CS
Chang
Huan-Yi
HY
Tseng
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000633:toxicity; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000633:toxicity*; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000633:toxicity*
D000970:Antineoplastic Agents; D007093:Imidazoles; D011744:Pyrimidinones