Discovery of α-Obscurine Derivatives as Novel Cav3.1 Calcium Channel Blockers

doi:10.1002/cbdv.202400182

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	Discovery of α-Obscurine Derivatives as Novel Cav3.1 Calcium Channel Blockers
	Wang, Lei; Li, Wen-Yan; Yuan, Zai-Feng; Zhao, Qin-Shi
	2024
发表期刊	CHEMISTRY & BIODIVERSITY
ISSN	1612-1872
卷号	21 期号:4 页码:-
摘要	Voltage-gated calcium channels (VGCCs), particularly T-type calcium channels (TTCCs), are crucial for various physiological processes and have been implicated in pain, epilepsy, and cancer. Despite the clinical trials of TTCC blockers like Z944 and MK8998, none are currently available on the market. This study investigates the efficacy of Lycopodium alkaloids, particularly as natural product-based TTCC blockers. We synthesized eighteen derivatives from alpha-obscurine, a lycodine-type alkaloid, and identified five derivatives with significant Ca(v)3.1 blockade activity. The most potent derivative, compound 7, exhibited an IC50 value of 0.19 perpendicular to 0.03 mu M and was further analyzed through molecular docking, revealing key interactions with Ca(v)3.1 . These findings provide a foundation for the structural optimization of Ca(v)3.1 calcium channel blockers and present compound 7 as a promising lead compound for drug development and a tool for chemical biology research.
DOI	10.1002/cbdv.202400182
WOS记录号	WOS:001168696700001
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/76259
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Wang, Lei,Li, Wen-Yan,Yuan, Zai-Feng,et al. Discovery of α-Obscurine Derivatives as Novel Cav3.1 Calcium Channel Blockers[J]. CHEMISTRY & BIODIVERSITY,2024,21(4):-.
APA	Wang, Lei,Li, Wen-Yan,Yuan, Zai-Feng,&Zhao, Qin-Shi.(2024).Discovery of α-Obscurine Derivatives as Novel Cav3.1 Calcium Channel Blockers.CHEMISTRY & BIODIVERSITY,21(4),-.
MLA	Wang, Lei,et al."Discovery of α-Obscurine Derivatives as Novel Cav3.1 Calcium Channel Blockers".CHEMISTRY & BIODIVERSITY 21.4(2024):-.

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