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Synthesis and Cytotoxic Activities of α ‐Methylidene‐ γ ‐butyrolactones Bearing a Quinolin‐4(1 H )‐one Moiety
Author(s) -
Hsu ShuLin,
Chen YehLong,
Tzeng CherngChyi,
Fang KuoChang,
Sheu JiaYuh
Publication year - 2001
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(20010418)84:4<874::aid-hlca874>3.0.co;2-i
Subject(s) - chemistry , moiety , piperazine , stereochemistry , cytotoxic t cell , alkylation , cytotoxicity , cell culture , in vitro , biochemistry , organic chemistry , biology , genetics , catalysis
The cytotoxicities of the α ‐methylidene‐ γ ‐butyrolactones 4 , 5 , and 8 , which are linked to a quinolin‐4(1 H )‐one moiety through a piperazine or O‐atom bridge were studied. These compounds were synthesized by alkylation of 1‐ethyl‐6‐fluoro‐1,4‐dihydro‐7‐hydroxy‐4‐oxoquinoline‐3‐carboxylic acid ( 6 ) followed by a Reformatsky ‐type condensation. Compounds 4 , 5 , and 8 were evaluated in vitro against 60 human‐tumor cell lines derived from nine cancer‐cell types and demonstrated not only strong growth‐inhibitory activities against leukemia cancer cells, but also fairly good activities against the growth of certain solid tumors (see Table ). The O‐bridged derivatives 8a and 8b exhibit both cytostatic (mean log GI 50 =−5.20 and −5.82, resp.) and cytocidal (mean log LC 50 =−4.30 and −4.93, resp.) effects, while the piperazine‐bridged analogues 4 and 5 possess only weak cytostatic (mean log GI 50 =−5.19 and −4.74, resp.; mean log LC 50 >−4.00) capability. Among them, 8b is the most potent, with log GI 50 =−6.47, −6.72, −6.53, and −6.52 against leukemia, SW‐620 (colon), Lox IMV1, and SK‐MEL‐28 (melanoma) cancer cells, respectively.