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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
Author(s) -
Lin ChiFong,
Lu WenDer,
Hsieh PeiChen,
Kuo YaoHaur,
Chiu HueyFen,
Wang ChyiJia,
Wu MingJung
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200208)85:8<2564::aid-hlca2564>3.0.co;2-0
Subject(s) - chemistry , cytotoxicity , hela , stereochemistry , ene reaction , benzonitrile , trifluoromethyl , topoisomerase , cell culture , medicinal chemistry , cell , enzyme , biochemistry , in vitro , organic chemistry , alkyl , genetics , biology
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 μ M . 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.