Synthesis and Cytotoxic Activities of α-Methylidene-γ-butyrolactones Bearing a Quinolin-4(1H)-one Moiety

✍ Scribed by Shu-Lin Hsu; Yeh-Long Chen; Cherng-Chyi Tzeng; Kuo-Chang Fang; Jia-Yuh Sheu

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: German
• Weight: 80 KB
• Volume: 84
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/1522-2675(20010418)84:4<874::aid-hlca874>3.0.co;2-i

✦ Synopsis

The cytotoxicities of the a-methylidene-g-butyrolactones 4, 5, and 8, which are linked to a quinolin-4(1H)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 À 5.20 and À 5.82, resp.) and cytocidal (mean log LC 50 À 4.30 and À 4.93, resp.) effects, while the piperazine-bridged analogues 4 and 5 possess only weak cytostatic (mean log GI 50 À 5.19 and À 4.74, resp.; mean log LC 50 bÀ 4.00) capability. Among them, 8b is the most potent, with log GI 50