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- Title
Geiparvarin Analogues: Synthesis and Anticancer Evaluation of α-Methylidene- γ-butyrolactone-Bearing Coumarins.
- Authors
Chen, Yeh-Long; Wang, Tai-Chi; Tzeng, Cherng-Chyi; Chang, Nein-Chen
- Abstract
To determine some of the structural features of geiparvarin that account for its cytostatic activity in vitro, certain geiparvarin analogues modified in the furan-3(2 H)-one moiety and the alkenyloxy substituent were synthesized and tested against the growth of 60 human cancer cell lines derived from nine cancer-cell types. These compounds demonstrated a strong growth-inhibitory activity against leukemia cell lines but were relatively inactive against non-small-cell lung cancers and CNS cancers. Comparison of the mean log GI50 values of γ-[( E)-1-methylprop-1-enyl]- α-methylidene- γ-butyrolactones 7 - 9 revealed that 7-[( E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy]-2 H- 1-benzopyran-2-one ( 8; −5.47) was more active than its 6-substituted counterpart 7 (−5.21) and its 3-chloro-4-methyl derivative 9 (−5.31) and had a potency similar to that of geiparvarin (log GI50=−5.41). These results indicated that the furan-3(2 H)-one moiety of geiparvarin could be replaced by an α-methylidene- γ-butyrolactone unit without losing the anticancer potency, and that the best substitution site at the coumarin moiety was C(7). The alkenyloxy substituent of 8 was also replaced by a methoxy substituent. Among these α-methylidene- γ-butyrolactones, 7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenylfuran-2-yl)methoxy]-2 H-1-benzopyran-2-one ( 11) was the most potent with a mean log GI50 value of −5.83 and a range value of 132 (102.12).
- Publication
Helvetica Chimica Acta, 1999, Vol 82, Issue 2, p191
- ISSN
0018-019X
- Publication type
Article
- DOI
10.1002/(SICI)1522-2675(19990210)82:2<191::AID-HLCA191>3.0.CO;2-P