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
| Autor: | Chi-Fong Lin, Pei-Chen Hsieh, Chyi-Jia Wang, Huey-Fen Chiu, Wen-Der Lu, Yao-Haur Kuo, Ming-Jung Wu |
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| Rok vydání: | 2002 |
| Předmět: |
Trifluoromethyl
biology Chemistry Stereochemistry Topoisomerase Organic Chemistry biology.organism_classification Biochemistry Catalysis Inorganic Chemistry HeLa Biological pathway Benzonitrile chemistry.chemical_compound Cell culture Drug Discovery biology.protein Physical and Theoretical Chemistry Cytotoxicity Ene reaction |
| Zdroj: | Helvetica Chimica Acta. 85:2564-2575 |
| ISSN: | 1522-2675 0018-019X |
| DOI: | 10.1002/1522-2675(200208)85:8<2564::aid-hlca2564>3.0.co;2-0 |
| Popis: | 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 (20) exhibits the strongest inhibitory activity with the Hela cell line. Derivatives 9, 10, 18, and 23 display inhibitory activities with topoisomerase I at 87 μM. 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. |
| Databáze: | OpenAIRE |
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