Synthesis and Cytotoxic Evaluation of a Series of γ-Substituted γ-Aryloxymethyl-α-methylene-γ-butyrolactones Against Cancer Cells
- 1 January 2000
- journal article
- Published by Springer Science and Business Media LLC in Pharmaceutical Research
- Vol. 17 (6), 715-719
- https://doi.org/10.1023/a:1007534416561
Abstract
Purpose. The main objective of this investigation was to explore thecytotoxic structure-activity relationships of γ-substituted γ-aryloxymethyl-α-methylene-γ-butyrolactones against cancer cells. Methods. The target compounds were synthesized in two stepscommencing with aryl-OH which was treated with a bromomethyl ketonefollowed by the Reformatsky-type condensation. Results. Seven types of α-methylene-γ-butyrolactones were evaluatedin vitro against 60 human cancer cell lines derived from nine cancercell types. The average values of log G50 indicated that for thearylportion, potencies of these α-methylene-γ-butyrolactones are in adecreasing order of quinolin-2(1H)-one (or 2-hydroxyquinoline, 21,−5.89) > quinoline (19, −5.79) > 2-methylquinoline (20, −5.69)> 8-hydroxyquinoline (17, −5.64) > 2-naphthalene (16, −5.59)> benzene (15, −4.90). The same order was obtained for both log TGIand log LC50. However, for the γ-substituent, the potencies are in adecreasing order of biphenyl (16f–21f) > phenyl and4-substituted phenyl (16b-e–21b-e) > methyl (16a–21a). Conclusions. Unlike cardiovascular activities of α-methylene-γ-butyrolactones in which a γ-methyl substituent is necessary for vasorelaxingeffect while a phenyl or a halogen-substituted phenyl is prefer for theantiplatelet activities, a γ-biphenyl substituent proved to be the bestfor their cytotoxicities against various cancer cell lines tested.Keywords
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