作者
Mary Hassani, Wen Cai, David C Holley, Jayana P Lineswala, Babu R Maharjan, G Reza Ebrahimian, Hassan Seradj, Mark G Stocksdale, Farahnaz Mohammadi, Christopher C Marvin, John M Gerdes, Howard D Beall, Mohammad Behforouz
发表日期
2005/12/1
期刊
Journal of medicinal chemistry
卷号
48
期号
24
页码范围
7733-7749
出版商
American Chemical Society
简介
Novel lavendamycin analogues with various substituents were synthesized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. Pictet−Spengler condensation of quinoline- or quninoline-5,8-dione aldehydes with tryptamine or tryptophans yielded the lavendamycins. Metabolism studies with recombinant human NQO1 revealed that addition of NH2 and CH2OH groups at the quinolinedione-7-position and indolopyridine-2‘-position had the greatest positive impact on substrate specificity. The best and poorest substrates were 37 (2‘-CH2OH-7-NH2 derivative) and 31 (2‘-CONH2-7-NHCOC3H7-n derivative) with reduction rates of 263 ± 30 and 0.1 ± 0.1 μmol/min/mg NQO1, respectively. Cytotoxicity toward human colon adenocarcinoma cells was determined for the lavendamycins. The best substrates for NQO1 were also the most selectively toxic to the NQO1-rich BE-NQ …
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M Hassani, W Cai, DC Holley, JP Lineswala… - Journal of medicinal chemistry, 2005