Antiproliferative Aspidosperma-Type Monoterpenoid Indole Alkaloids from Bousigonia mekongensis Inhibit Tubulin Polymerization

doi:10.3390/molecules24071256

	Antiproliferative Aspidosperma-Type Monoterpenoid Indole Alkaloids from Bousigonia mekongensis Inhibit Tubulin Polymerization
	Zhang, Yu1,2 ; Goto, Masuo 2; Oda, Akifumi 3; Hsu, Pei-Ling 2; Guo, Ling-Li1 ; Fu, Yan-Hui1 ; Morris-Natschke, Susan L.2; Hamel, Ernest 4; Lee, Kuo-Hsiung 2,5; Hao, Xiao-Jiang1
通讯作者	Goto, Masuo(goto@med.unc.edu) ; Lee, Kuo-Hsiung(khlee@unc.edu) ; Hao, Xiao-Jiang(haoxj@mail.kib.ac.cn)
	2019-03-31
发表期刊	MOLECULES
ISSN	1420-3049
卷号	24 期号:7 页码:10
摘要	Monoterpenoid 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.
关键词	aspidosperma-type monoterpenoid indole alkaloids antiproliferative activity tubulin inhibitor Bousigonia mekongensis
DOI	10.3390/molecules24071256
收录类别	SCI
语种	英语
WOS记录号	WOS:000464962900002
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/67607
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Goto, Masuo; Lee, Kuo-Hsiung; Hao, Xiao-Jiang
作者单位	1.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
推荐引用方式 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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