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7221491 
Journal Article 
Alkyne-substituted diminazene as G-quadruplex binders with anticancer activities 
Wang, C; Carter-Cooper, B; Du, Y; Zhou, J; Saeed, MA; Liu, J; Guo, M; Roembke, B; Mikek, C; Lewis, EA; Lapidus, RG; Sintim, HO; , 
2016 
Yes 
European Journal of Medicinal Chemistry
ISSN: 0223-5234
EISSN: 1768-3254 
English 
27132164 
G-quadruplex ligands have been touted as potential anticancer agents, however, none of the reported G-quadruplex-interactive small molecules have gone past phase II clinical trials. Recently it was revealed that diminazene (berenil, DMZ) actually binds to G-quadruplexes 1000 times better than DNA duplexes, with dissociation constants approaching 1 nM. DMZ however does not have strong anticancer activities. In this paper, using a panel of biophysical tools, including NMR, FRET melting assay and FRET competition assay, we discovered that monoamidine analogues of DMZ bearing alkyne substitutes selectively bind to G-quadruplexes. The lead DMZ analogues were shown to be able to target c-MYC G-quadruplex both in vitro and in vivo. Alkyne DMZ analogues display respectable anticancer activities (single digit micromolar GI50) against ovarian (OVCAR-3), prostate (PC-3) and triple negative breast (MDA-MB-231) cancer cell lines and represent interesting new leads to develop anticancer agents.