title: Synthesis and evaluation of cationic phthalocyanine derivatives as potential inhibitors of telomerase.
abstract: 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.
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University, Hubei, Wuhan 430072, PR China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Lige
authors.initials: L
authors.lastname: Ren
authors.forename: Minghui
authors.initials: M
authors.lastname: Bai
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Baoping
authors.initials: B
authors.lastname: Zhai
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D054833:Isoindoles; D019098:Telomerase; C013647:phthalocyanine