title: Bioassay-guided isolation of an alkaloid with antiangiogenic and antitumor activities from the extract of Fissistigma cavaleriei root.
abstract: Fissistigma cavaleriei (Levl) Rehd (Annonaceae) is used as a folklore medicine for treatment of inflammation, arthritis, and tuberculosis by Miao people in China. In the present study, the antiangiogenic activity of F. cavaleriei was investigated. The chorioallantoic membrane of the fertilized hen's egg (CAM assay) was used to determine antiangiogenic activity of the plant extract. Compound (1), a compound with antiangiogenic activity, was isolated by bioassay-guided fractionation from F. cavaleriei for the first time. The structure of compound (1) was elucidated on the basis of spectroscopic methods. Colorimetric COX (ovine) inhibitor screening assay was used to determine its inhibitory effect on COX-1 and COX-2. MTT and Sulforhodamine B assays were used to investigate its cytotoxic effects on tumor cell lines. As a result, compound (1) showed a selectively inhibiting effect on COX-2 and could inhibit the growth of tumor cells in vitro. The antitumor activity of compound (1) was further confirmed by the observation that compound (1) administration significantly inhibited the growth of S-180 cells in mice. Moreover, compound (1) was able to enhance the antitumor activity of doxorubicin in the mice bearing with S-180 cells while combined with doxorubicin. In conclusion, compound (1) is a multi-target molecule and further experimental investigations are needed to determine whether it can be used as a lead molecule for tumor treatment.
authors.affiliation: Department of Bioengineering, School of Chemistry and Chemical Engineering, Guizhou University, Guiyang 550003, PR China. yangzaichang@126.com
authors.forename: Zaichang
authors.initials: Z
authors.lastname: Yang
authors.forename: Weilun
authors.initials: W
authors.lastname: Lu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ma
authors.forename: Dandan
authors.initials: D
authors.lastname: Song
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D029061:Annonaceae / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001681:Biological Assay / Q000379:methods*; D005591:Chemical Fractionation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000737:chemistry / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005562:Formazans / Q000737:chemistry; D006801:Humans; D054833:Isoindoles / Q000494:pharmacology; D020014:K562 Cells; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry; D013778:Tetrazolium Salts / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: C572383:(5-methoxy-2-methylisoindolin-1-yl)(4-methoxyphenyl)methanol; D000470:Alkaloids; D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D052246:Cyclooxygenase 2 Inhibitors; D005562:Formazans; D054833:Isoindoles; D010936:Plant Extracts; D012235:Rhodamines; D013778:Tetrazolium Salts; C079782:MTT formazan; C022027:lissamine rhodamine B; D004317:Doxorubicin; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human