title: Optimized conversion of antiproliferative lignans pinoresinol and epipinoresinol: Their simultaneous isolation and identification by centrifugal partition chromatography and high performance liquid chromatography.
abstract: High amount of the valuable lignan pinoresinol (PR) was determined in Carduus nutans fruit (7.8mg/g) for the first time. A preparative separation method using two consecutive, identical steps of centrifugal partition chromatography (CPC) was developed in order (i) to isolate PR and (ii) to subsequently isolate PR and its 7' epimer epipinoresinol (EPR) simultaneously after an optimized acid treatment which resulted in PR epimerization forming equal amounts of PR and EPR, from C. nutans fruit. As optimal conditions, a two-phase solvent system consisting of methyl tert-butyl ether:acetone:water (4:3:3, v/v/v) for CPC separation, and an acid treatment performed at 50°C for 30min for the epimerization were applied. Thus, 33.7mg and 32.8mg PR and EPR, in as high as 93.7% and 92.3% purity, were isolated from 10.0gC. nutans fruit, representing 86.4% and 84.1% efficiency, respectively. Conversion characteristic of PR and EPR in acidic medium, determined as a function of time and temperature of acid treatment provides their unambiguous identification by on-line high performance liquid chromatography (HPLC). Antiproliferative assay of isolated PR and EPR in two different types of colon cancer cell lines (HCT116 and SW480) confirmed that both epimers caused a more significant decrease of viability in HCT116 cells than in SW480 cells, suggesting their similar mechanism of antiproliferative action.
authors.affiliation: Department of Pharmacognosy, Semmelweis University, 1085 Budapest, Üllői út 26, Hungary.
authors.forename: Anna
authors.initials: A
authors.lastname: Sólyomváry
authors.affiliation: Department of Pharmacognosy, Semmelweis University, 1085 Budapest, Üllői út 26, Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Alberti
authors.affiliation: Department of Pharmacognosy, Semmelweis University, 1085 Budapest, Üllői út 26, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Darcsi
authors.affiliation: Department of Pharmacognosy, Semmelweis University, 1085 Budapest, Üllői út 26, Hungary; Department of Plant Anatomy, Eötvös Lóránd University, 1117 Budapest, Pázmány Péter sétány 1/C, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Könye
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hőgyes Endre u. 9, Hungary.
authors.forename: Gergő
authors.initials: G
authors.lastname: Tóth
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hőgyes Endre u. 9, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
authors.affiliation: Institute of Chemistry, Eötvös Lóránd University, 1117 Budapest, Pázmány Péter sétány 1/A, Hungary.
authors.forename: Ibolya
authors.initials: I
authors.lastname: Molnár-Perl
authors.affiliation: RotaChrom Technologies Ltd., 2370 Dabas, Fő út 151, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Lorántfy
authors.affiliation: Vichem Chemie Research Ltd., 1022 Budapest, Herman Ottó út 15, Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Dobos
authors.affiliation: Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hőgyes Endre u. 9, Hungary; Vichem Chemie Research Ltd., 1022 Budapest, Herman Ottó út 15, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Őrfi
authors.affiliation: Department of Pharmacognosy, Semmelweis University, 1085 Budapest, Üllői út 26, Hungary.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Béni
authors.affiliation: Department of Plant Anatomy, Eötvös Lóránd University, 1117 Budapest, Pázmány Péter sétány 1/C, Hungary. Electronic address: boldizsarimi@gmail.com.
authors.forename: Imre
authors.initials: I
authors.lastname: Boldizsár
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology; D031177:Carduus / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003110:Colonic Neoplasms / Q000188:drug therapy; D005638:Fruit / Q000737:chemistry; D005663:Furans / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D017705:Lignans / Q000032:analysis* / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D017705:Lignans; D010936:Plant Extracts; C103298:pinoresinol
keywords: Centrifugal partition chromatography; Colon cancer; Epipinoresinol; HPLC; Isolation; Pinoresinol