Premium
Synthesis and Cytotoxicity Evaluation of Certain α ‐Methylidene‐ γ ‐butyrolactones Bearing Coumarin, Flavone, Xanthone, Carbazole, and Dibenzofuran Moieties
Author(s) -
Chen YehLong,
Chen ILi,
Tzeng CherngChyi,
Wang TaiChi
Publication year - 2000
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/(sici)1522-2675(20000510)83:5<989::aid-hlca989>3.0.co;2-e
Subject(s) - chemistry , xanthone , dibenzofuran , carbazole , substituent , coumarin , stereochemistry , acridine , cytotoxicity , pyrazine , in vitro , organic chemistry , biochemistry
The cytotoxicities of α ‐methylidene‐ γ ‐butyrolactones, which are linked to coumarins (see 15 and 16 ) and to potential DNA‐intercalating carriers such as flavones, xanthones, carbazole, and dibenzofuran (see 9a – e , 10a – e , 11 , and 12 ), were studied. These compounds were synthesized via alkylation of their hydroxy precursors followed by a Reformatsky‐ type condensation ( Scheme ). These α ‐methylidene‐ γ ‐butyralactones were evaluated in vitro against 60 human tumor cell lines derived from nine cancer cell types and demonstrated a strong growth‐inhibitory activity against leukemia cancer cells ( Tables 1 and 2 ). For flavone‐ and xanthone‐containing α ‐methylidene‐ γ ‐butyrolactones 9a – e and 10a – e , respectively, the overall potency (mean value) decreased on introduction of an electron‐withdrawing substituent at the γ ‐phenyl substituent and increased with an electron‐donating substituent. Comparing the different chromophores established the following order of decreasing potency (log GI 50 ): dibenzofuran ( 12 , −6.17) > flavone ( 9a , −5.96) > carbazole ( 11 , −5.80) and xanthone ( 10a , −5.77) > coumarin ( 15 , −5.60; 16 , −5.65). Among them, the dibenzofuran derivative 12 showed not only strong inhibitory activities against leukemia cancer cell lines with an average log GI 50 value of −7.22, but also good inhibitory activities against colon, melanoma, and breast cancer cells with average log GI 50 values of −6.23, −6.31, and −6.39, respectively.