title: Direct screening of G-quadruplex ligands from Kalopanax septemlobus (Thunb.) Koidz extract by high performance liquid chromatography.
abstract: G-quadruplex DNA structure is considered to be a very attractive target for antitumor drug design due to its unique role in maintaining telomerase activities. Therefore, discovering ligands with high stability of G-quadruplex structure is of great interest. In this paper, high-performance liquid chromatography (HPLC) was used for fast screening of G-quadruplex ligands from the crude extract of Kalopanax septemlobus (Thunb.) Koidz, a traditional Chinese medicine. Four potent G-quadruplex ligands were firstly selected through HPLC by comparing the peak profiles and absorption intensity of the crude sample before and after interaction with G-quadruplex DNA. Then the target compounds were isolated and purified by high-speed countercurrent chromatography (HSCCC) for further confirmation of their stabilities of G-quadruplex by temperature-dependent circular dichroism (CD). Four compounds were isolated and identified as 2,4-dihydroxybenzoic acid (I), chlorogenic acid (II), caffeic acid (III) and 5-feruloylquinic acid (IV) each by MS and NMR. Finally, compound I, II, III were each proved to be potent G-quadruplex ligands by decreasing the peak intensity in HPLC chromatogram after complexation with G-quadruplex, which stabilize G-quadruplex by 7±2 °C, 10±2 °C, and 3±2 °C respectively, based on CD analyses. However, compound IV showed no G-quadruplex stability. The decrease of peak absorption intensity in HPLC chromatogram is the most important signal to find G-quadruplex ligands. This provides a very promising strategy for fast screening G-quadruplex ligands from natural plant extracts.
authors.affiliation: Beijing Key Laboratory of Plant Resources Research and Development, Beijing Technology and Business University, Beijing 100048, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Bai
authors.forename: Xueli
authors.initials: X
authors.lastname: Cao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Junfeng
authors.initials: J
authors.lastname: Xiang
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.forename: Yalin
authors.initials: Y
authors.lastname: Tang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003373:Coumaric Acids / Q000737:chemistry* / Q000378:metabolism; D003377:Countercurrent Distribution; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes; D062385:Hydroxybenzoates / Q000737:chemistry* / Q000378:metabolism; D036882:Kalopanax / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000970:Antineoplastic Agents; D003373:Coumaric Acids; D004365:Drugs, Chinese Herbal; D062385:Hydroxybenzoates; C017704:beta-resorcylic acid