title: Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium.
abstract: Five new phorbol esters, (four phorbol diesters, 1-4, and one 4-deoxy-4α-phorbol diester, 5), as well as four known phorbol esters analogues (6-9) were isolated and identified from the branches and leaves of Croton tiglium. Their structures were elucidated mainly by extensive NMR spectroscopic, and mass spectrometric analysis. Among them, compound (1) was the first example of a naturally occurring phorbol ester with the 20-aldehyde group. Compounds 2-5, and 7-9 showed potent cytotoxicity against the K562, A549, DU145, H1975, MCF-7, U937, SGC-7901, HL60, Hela, and MOLT-4 cell lines, with IC50 values ranging from 1.0 to 43 μM, while none of the compounds exhibited cytotoxic effects on normal human cell lines 293T and LX-2, respectively. In addition, compound 3 exhibited moderate COX-1 and COX-2 inhibition, with IC50 values of 0.14 and 8.5 μM, respectively.
authors.affiliation: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China; CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China.
authors.forename: Sheng-Hui
authors.initials: SH
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China.
authors.forename: Yan-Qun
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha 410208, PR China.
authors.forename: Din-Xiang
authors.initials: DX
authors.lastname: Li
authors.affiliation: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: He
authors.affiliation: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica/RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China. Electronic address: yonghongliu@scsio.ac.cn.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, PR China. Electronic address: gale9888@163.com.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Zhou
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D029802:Croton / Q000737:chemistry*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D010703:Phorbol Esters / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D010703:Phorbol Esters; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory activity; Croton tiglium; Cytotoxicity; Phorbol esters