title: Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria.
abstract: Eight new cardiac glycosides/aglycones (antiaritoxiosides A-G, 1-7, and antiarotoxinin B, 8), two new coumarins (anticarins A-B, 41-42), and two new flavanones (antiarones L-K, 43-44) were isolated from trunk bark of Antiaris toxicaria together with 53 known compounds. The new structures were established by extensive analysis of spectroscopic data. Compound 1 (10-carboxy and 3α-hydroxy) and compounds 3-6 (10-hydroxy) contain unique substituents that are rarely found in cardiac glycosides. The cytotoxic effects of isolated compounds against ten human cancer cell lines, KB, KB-VIN, A549, MCF-7, U-87-MG, PC-3, 1A9, CAKI-1, HCT-9 and S-KMEL-2, were tested using the sulforhodamine B assay. Five compounds (12, 16, 20, 22, and 31) showed significant cytotoxicity against all ten cancer cell lines, with notable potency at the ng/mL level against some cell lines, which merits further development as clinical trial candidates.
authors.affiliation: Department of Biotechnology, National Formosa University, Yunlin 632, Taiwan; Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: Li-Shian
authors.initials: LS
authors.lastname: Shi
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 401, Taiwan.
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.affiliation: Kunming Institute of Botany, Chinese Academy of Science, Kunming 650204, Yunnan, China.
authors.forename: Han-Dong
authors.initials: HD
authors.lastname: Sun
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA; Department of Pharmacy and Chinese Medicine Research and Development Center, China Medical University, Taichung 401, Taiwan.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599-7568, USA. Electronic address: tswu@mail.ncku.edu.tw.
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
mesh_terms: D031621:Antiaris / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002301:Cardiac Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D024301:Plant Bark / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002301:Cardiac Glycosides; D003374:Coumarins
keywords: Antiaris toxicaria; Cardiac glycosides; Coumarins; Cytotoxicity