Antiproliferative Aspidosperma-Type Monoterpenoid Indole Alkaloids from Bousigonia mekongensis Inhibit Tubulin Polymerization
Zhang, Yu1,2; Goto, Masuo2; Oda, Akifumi3; Hsu, Pei-Ling2; Guo, Ling-Li1; Fu, Yan-Hui1; Morris-Natschke, Susan L.2; Hamel, Ernest4; Lee, Kuo-Hsiung2,5; Hao, Xiao-Jiang1
Corresponding AuthorGoto, Masuo(goto@med.unc.edu) ; Lee, Kuo-Hsiung(khlee@unc.edu) ; Hao, Xiao-Jiang(haoxj@mail.kib.ac.cn)
2019-03-31
Source PublicationMOLECULES
ISSN1420-3049
Volume24Issue:7Pages:10
AbstractMonoterpenoid indole alkaloids are structurally diverse natural products found in plants of the family Apocynaceae. Among them, vincristine and its derivatives are well known for their anticancer activity. Bousigonia mekongensis, a species in this family, contains various monoterpenoid indole alkaloids. In the current study, fourteen known aspidosperma-type monoterpenoid indole alkaloids (1-14) were isolated and identified from a methanol extract of the twigs and leaves of B. mekongensis for the first time. Among them, compounds 3, 6, 9, and 13 exhibited similar antiproliferative activity spectra against A549, KB, and multidrug-resistant (MDR) KB subline KB-VIN cells with IC50 values ranging from 0.5-0.9 mu M. The above alkaloids efficiently induced cell cycle arrest at the G2/M phase by inhibiting tubulin polymerization as well as mitotic bipolar spindle formation. Computer modeling studies indicated that compound 7 likely forms a hydrogen bond (H-bond) with alpha- or beta-tubulin at the colchicine site. Evaluation of the antiproliferative effects and SAR analysis suggested that a 14,15-double bond or 3 alpha-acetonyl group is critical for enhanced antiproliferative activity. Mechanism of action studies demonstrated for the first time that compounds 3, 4, 6, 7, and 13 efficiently induce cell cycle arrest at G2/M by inhibiting tubulin polymerization by binding to the colchicine site.
Keywordaspidosperma-type monoterpenoid indole alkaloids antiproliferative activity tubulin inhibitor Bousigonia mekongensis
DOI10.3390/molecules24071256
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Chemistry
WOS SubjectBiochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS IDWOS:000464962900002
Citation statistics
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/67607
Collection植物化学与西部植物资源持续利用国家重点实验室
Corresponding AuthorGoto, Masuo; Lee, Kuo-Hsiung; Hao, Xiao-Jiang
Affiliation1.Chinese Acad Sci, Kunming Inst Bot, Key Lab Phytochem & Plant Resources West China, Kunming 650201, Yunnan, Peoples R China
2.Univ N Carolina, UNC Eshelman Sch Pharm, Nat Prod Res Labs, Chapel Hill, NC 27599 USA
3.Meijo Univ, Grad Sch Pharm, Tempaku Ku, 150 Yagotoyama, Nagoya, Aichi 4688503, Japan
4.NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA
5.China Med Univ & Hosp, Chinese Med Res & Dev Ctr, 2 Yuh Der Rd, Taichung 40447, Taiwan
Recommended Citation
GB/T 7714
Zhang, Yu,Goto, Masuo,Oda, Akifumi,et al. Antiproliferative Aspidosperma-Type Monoterpenoid Indole Alkaloids from Bousigonia mekongensis Inhibit Tubulin Polymerization[J]. MOLECULES,2019,24(7):10.
APA Zhang, Yu.,Goto, Masuo.,Oda, Akifumi.,Hsu, Pei-Ling.,Guo, Ling-Li.,...&Hao, Xiao-Jiang.(2019).Antiproliferative Aspidosperma-Type Monoterpenoid Indole Alkaloids from Bousigonia mekongensis Inhibit Tubulin Polymerization.MOLECULES,24(7),10.
MLA Zhang, Yu,et al."Antiproliferative Aspidosperma-Type Monoterpenoid Indole Alkaloids from Bousigonia mekongensis Inhibit Tubulin Polymerization".MOLECULES 24.7(2019):10.
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