School of Pharmaceutical Sciences, Sun Yat-sen University, Waihuan East Road 132, Guangzhou 510080, People's Republic of China.
Eur J Med Chem. 2011 May;46(5):1906-13. doi: 10.1016/j.ejmech.2011.02.020. Epub 2011 Feb 22.
A series of quinolino-benzo-[5, 6]-dihydroisoquindolium compounds (3a, 3f, 3g, and 3j) derived from alkaloid berberine were designed and synthesized as novel G-quadruplex ligands. Subsequent biophysical and biochemical evaluation demonstrated that the addition of pyridine ring and amino group into berberine improved the binding ability and selectivity towards G-quadruplex DNA in comparison with the previously reported 9-N-substituted berberine derivatives. Furthermore, qRT-PCR assay showed compound 3j led the down-regulation of c-myc gene transcription in leukemia cell line HL60, while little effect on normal cell line ECV-304, which was consistent with the behavior of an effective G-quadruplex ligand targeting c-myc oncogene.
一系列源于生物碱小檗碱的喹啉并苯并[5,6]-二氢异喹啉化合物（3a、3f、3g 和 3j）被设计并合成作为新型 G-四链体配体。随后的生物物理和生化评估表明，与之前报道的 9-N-取代小檗碱衍生物相比，在小檗碱中引入吡啶环和氨基可以提高其与 G-四链体 DNA 的结合能力和选择性。此外，qRT-PCR 实验表明，化合物 3j 可下调白血病细胞系 HL60 中的 c-myc 基因转录，而对正常细胞系 ECV-304 几乎没有影响，这与靶向 c-myc 癌基因的有效 G-四链体配体的行为一致。
