title: Diterpenoids from Wedelia prostrata and Their Derivatives and Cytotoxic Activities.
abstract: One new ent-kaurane diterpenoid, 11β,16α-dihydroxy-ent-kauran-19-oic acid (1), together with eight known analogues 2 - 9 were isolated from the aerial parts of Wedelia prostrata. One of the acidic diterpenoids, kaurenoic acid (3), was converted to seven derivatives, 10 - 16. All compounds were evaluated for their cytotoxic activity in vitro against human leukemia (K562), liver (HepG-2), and stomach (SGC-7901) cancer cell lines. Only four kaurenoic acid derivatives, 13 - 16, with 15-keto and substitutions at C(19) position, exhibited notable cytotoxic activities on these tumor cell lines with IC50value ranging from 0.05 to 3.71 μm. Compounds 10 - 12, with oxime on C(15) showed moderate inhibitory effects and compounds 1 - 9 showed no cytotoxicities on them. Structure-activity relationships were also discussed based on the experimental data obtained. The known derivative, 15-oxokaurenoic acid 4-piperdin-1-ylbutyl ester (17), induced typical apoptotic cell death in colon SW480 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis.
authors.affiliation: Key Laboratory of Natural Drug Pharmacology in Fujian Province, School of Pharmacy, Fujian Medical University, 88 Jiao Tong Road, Fuzhou, 350004, P. R. China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Ma
authors.affiliation: Key Laboratory of Natural Drug Pharmacology in Fujian Province, School of Pharmacy, Fujian Medical University, 88 Jiao Tong Road, Fuzhou, 350004, P. R. China.
authors.forename: Zhi-Biao
authors.initials: ZB
authors.lastname: Wang
authors.affiliation: Key Laboratory of Natural Drug Pharmacology in Fujian Province, School of Pharmacy, Fujian Medical University, 88 Jiao Tong Road, Fuzhou, 350004, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Drug Pharmacology in Fujian Province, School of Pharmacy, Fujian Medical University, 88 Jiao Tong Road, Fuzhou, 350004, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Key Laboratory of Natural Drug Pharmacology in Fujian Province, School of Pharmacy, Fujian Medical University, 88 Jiao Tong Road, Fuzhou, 350004, P. R. China.
authors.forename: Cui-Min
authors.initials: CM
authors.lastname: Deng
authors.affiliation: Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005, P. R. China.
authors.forename: Tian-Hua
authors.initials: TH
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen, 361005, P. R. China.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Li
authors.affiliation: Key Laboratory of Natural Drug Pharmacology in Fujian Province, School of Pharmacy, Fujian Medical University, 88 Jiao Tong Road, Fuzhou, 350004, P. R. China.
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Natural Drug Pharmacology in Fujian Province, School of Pharmacy, Fujian Medical University, 88 Jiao Tong Road, Fuzhou, 350004, P. R. China.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000302:isolation & purification* / Q000633:toxicity*; D045786:Diterpenes, Kaurane / Q000302:isolation & purification; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D035261:Plant Components, Aerial / Q000737:chemistry; D013329:Structure-Activity Relationship; D031209:Wedelia / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D045786:Diterpenes, Kaurane; C051436:kaurenoic acid
keywords: 
  Wedelia prostrata
  ; Apoptosis-inducing activities; Asteraceae; Cytotoxic activities; ent-Kaurane diterpenoid