Quinolino-benzo-[5, 6]-dihydroisoquindolium compounds derived from berberine: A new class of highly selective ligands for G-quadruplex DNA in c-myc oncogene

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.

Graphical abstractA series of quinolino-benzo-[5, 6]-dihydroisoquindolium derivatives (3a, 3f, 3g, and 3j) was designed, synthesized and evaluated as new G-quadruplex ligands.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A series of quinolino-benzo-[5, 6]-dihydroisoquindolium compounds derived from alkaloid berberine were synthesized. ► The addition of pyridine ring and amino group into berberine improved the binding ability and selectivity towards G-quadruplex DNA. ► 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.