Structurally modified Cyclovirobuxine-D Buxus alkaloids as effective analgesic agents through Cav3.2 T-Type calcium channel inhibition

doi:10.1016/j.bioorg.2023.106493

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	Structurally modified Cyclovirobuxine-D Buxus alkaloids as effective analgesic agents through Cav3.2 T-Type calcium channel inhibition
	Munikishore,Rachakunta; Liu,Rui; Zhang,Shuqun; Zhao,Qin-Shi; Nian,Yin; Zuo,Zhili
	2023
发表期刊	BIOORGANIC CHEMISTRY
ISSN	1090-2120
卷号	135 页码:106493
摘要	Cyclovirobuxine-D (CVB-D) is a Buxus alkaloid and a major active constituent in the Chinese medicinal herb Buxus microphylls. Traditionally, the natural alkaloid cyclovirobuxine-D has a long history of use as a traditional Chinese medicine for cardiovascular diseases as well as to treat a wide variety of medical conditions. As we found that CVB-D inhibited T-type calcium channels, we designed and synthesized a variety of fragments and analogues and evaluated them for the first time as new Cav3.2 inhibitors. Compounds 2-7 exhibited potency against Cav 3.2 channels, and two of them were more active than their parent molecules. As a result of the in vivo experiments, both compounds 3 and 4 showed significantly reduced writhes in the acetic acid-induced writhing test. Studies of molecular modeling have identified possible mechanism(s) of Cav3.2 binding. Moreover, the relationship be-tween structure and activity was studied in a preliminary manner. Our results indicated that compounds 3 and 4 could play an important role in the discovery and development of novel analgesics.
关键词	Buxus alkaloid Structural modification T -type calcium channel Analgesic activity Docking analysis Structure -activity relationship study BUXOZINE-C SEMPERVIRENS RING CONSTITUTION
学科领域	Biochemistry & Molecular Biology ; Chemistry
DOI	10.1016/j.bioorg.2023.106493
收录类别	SCI
WOS记录号	WOS:000967346200001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75478
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Munikishore,Rachakunta,Liu,Rui,Zhang,Shuqun,et al. Structurally modified Cyclovirobuxine-D Buxus alkaloids as effective analgesic agents through Cav3.2 T-Type calcium channel inhibition[J]. BIOORGANIC CHEMISTRY,2023,135:106493.
APA	Munikishore,Rachakunta,Liu,Rui,Zhang,Shuqun,Zhao,Qin-Shi,Nian,Yin,&Zuo,Zhili.(2023).Structurally modified Cyclovirobuxine-D Buxus alkaloids as effective analgesic agents through Cav3.2 T-Type calcium channel inhibition.BIOORGANIC CHEMISTRY,135,106493.
MLA	Munikishore,Rachakunta,et al."Structurally modified Cyclovirobuxine-D Buxus alkaloids as effective analgesic agents through Cav3.2 T-Type calcium channel inhibition".BIOORGANIC CHEMISTRY 135(2023):106493.

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