9-Substituted berberine derivatives as G-quadruplex stabilizing ligands in telomeric DNA.
The interaction of berberine and its 9-substituted derivatives with human telomeric DNA d[G(3)(T(2)AG(3))(3)](telo21) has been investigated via CD spectroscopy, fluorescence spectroscopy, PCR-stop assay, competitive dialysis, and telomerase repeat amplification protocol (TRAP) assay. The results indicated that these semisynthesized compounds could induce and stabilize the formation of anti-parallel G-quadruplex of telomeric DNA in the presence or absence of metal cations. Compared with berberine, the 9-substituted derivatives exhibit stronger binding affinity with G-quadruplex and higher inhibitory activity for telomerase. Introduction of a side chain with proper length of methylene and terminal amino group to the 9-position of berberine would significantly strengthen the binding affinity with G-quadruplex, resulting in increasing inhibitory effects on the amplification of telo21 DNA and on the telomerase activity.
Zhang
Wan-Jin
WJ
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China.
Ou
Tian-Miao
TM
Lu
Yu-Jing
YJ
Huang
Ying-Yu
YY
Wu
Wei-Bin
WB
Huang
Zhi-Shu
ZS
Zhou
Jin-Lin
JL
Wong
Kwok-Yin
KY
Gu
Lian-Quan
LQ
D001599:Berberine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054856:G-Quadruplexes; D005784:Gene Amplification / Q000235:genetics; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D008670:Metals / Q000737:chemistry; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D002412:Cations; D008024:Ligands; D008670:Metals; D001599:Berberine; D004247:DNA; D019098:Telomerase