Cytotoxicities and Topoisomerase I Inhibitory Activities of 2-[2-(2-Alkynylphenyl)ethynyl]benzonitriles, 1-Aryldec-3-ene-1,5-diynes, and Related Bis(enediynyl)arene Compounds
✍ Scribed by Chi-Fong Lin; Wen-Der Lu; Pei-Chen Hsieh; Yao-Haur Kuo; Huey-Fen Chiu; Chyi-Jia Wang; Ming-Jung Wu
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- German
- Weight
- 153 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
The activities of a series of acyclic enediynes, 2-(6-substituted hex-3-ene-1,5-diynyl)benzonitriles (1 ± 5) and their derivatives 7 ± 23 were evaluated against several solid tumor cell lines and topoisomerase I. Compounds 1 ± 5 show selective cytotoxicity with Hepa cells, and 2-[6-phenylhex-3-ene-1,5-diynyl]benzonitrile (5) reveals the most-potent activity. Analogues 8 ± 10 and 13 ± 22 also have the same effect with DLD cells; 1-[(Z)-dec-3-ene-1,5-diynyl)-4-nitrobenzene 21 shows the highest activity among them. Moreover, 1-[(Z)-dec-3-ene-1,5-diynyl]-2-(trifluoromethyl)benzene ( ) exhibits the strongest inhibitory activity with the Hela cell line. Derivatives 9, 10, 18, and 23 display inhibitory activities with topoisomerase I at 87 mm. The cell-cycle analysis of compound 5, which induces a significant blockage in S phase, indicates that these novel enediynes probably undergo other biological pathways leading to the cytotoxicity, except the inhibitory activity toward topoisomerase I.