ISSN:
1573-904X
Keywords:
α-methylene-γ-butyrolactones
;
cytotoxicity
;
quinolin-2(1H)-one
;
quinoline
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007534416561
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