Synthesis and evaluation of cationic phthalocyanine derivatives as potential inhibitors of telomerase.
A series of water-soluble cationic phthalocyanine derivatives (1-10) were designed and synthesized to develop novel and potent telomerase inhibitors. These phthalocyanine derivatives as inhibitors of telomerase were investigated via modified telomerase repeat amplification protocol (TRAP) assay. The TRAP assay indicates that these cationic compounds had strong telomerase inhibitory activity (IC(50)<1.65 microM). To determine whether the phthalocyanine derivatives binding to G-quadruplex enhance the block to DNA synthesis, primer extension reactions were carried out in the presence of phthalocyanines. The interaction of the G-quadruplex of telomerase DNA with these molecules was examined by CD melting and PCR stop assay. These cationic phthalocyanine derivatives can stabilize G-quadruplex, which is demonstrated by the increased T(m) values. All these results indicate that the phthalocyanine derivatives might be potential lead compounds for the development of new telomerase inhibitor.
Zhang
Lixia
L
College of Chemistry and Molecular Sciences, Wuhan University, Hubei, Wuhan 430072, PR China.
Huang
Jing
J
Ren
Lige
L
Bai
Minghui
M
Wu
Lin
L
Zhai
Baoping
B
Zhou
Xiang
X
D002942:Circular Dichroism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D054856:G-Quadruplexes / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D054833:Isoindoles; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors*; D013696:Temperature
D004791:Enzyme Inhibitors; D007211:Indoles; D054833:Isoindoles; D019098:Telomerase; C013647:phthalocyanine