Bialorastins A-F, highly oxygenated and polycyclic andrastin-type meroterpenoids with proangiogenic activity from the deep-sea cold-seep-derived fungus Penicillium bialowiezense CS-283

doi:10.1016/j.bioorg.2023.107073

CORC > 海洋研究所 > 中国科学院海洋研究所 > 实验海洋生物学重点实验室

	Bialorastins A-F, highly oxygenated and polycyclic andrastin-type meroterpenoids with proangiogenic activity from the deep-sea cold-seep-derived fungus Penicillium bialowiezense CS-283
	Yan, Li-Hong 3,4; Li, Pei-Hai 1; Li, Xiao-Ming 3; Yang, Sui-Qun 3; Liu, Ke-Chun 1; Zhang, Yun 1; Wang, Bin-Gui 3,4; Li, Xin 2,3
刊名	BIOORGANIC CHEMISTRY
	2024-02-01
卷号	143 页码:12
关键词	Cold-seep Penicillium bialowiezense Meroterpenoids Proangiogenic activity
ISSN号	0045-2068
DOI	10.1016/j.bioorg.2023.107073
通讯作者	Wang, Bin-Gui(wangbg@ms.qdio.ac.cn) ; Li, Xin(lixin@qdio.ac.cn)
英文摘要	Six new highly oxygenated and polycyclic andrastin-type meroterpenoids, namely, bialorastins A-F (1-6), were discovered from the culture of Penicillium bialowiezense CS-283, a fungus isolated from the deep-sea cold seep squat lobster Shinkaia crosnieri. The planar structures and absolute configurations of these compounds were determined by detailed analysis of spectroscopic data, single crystal X-ray diffraction, and TDDFT-ECD calculations. Structurally, bialorastin A (1) represents a rare 17-nor-andrastin that possesses an unusual 2-oxaspiro [4.5]decane-1,4-dione moiety with a unique 6/6/6/6/5 polycyclic system, while bialorastin B (2) is also a 17nor-andrastin featuring a gem-propane-1,2-dione moiety. Additionally, bialorastins C-E (3-5) possess a 6/6/6/6/ 5/5 fused hexacyclic skeleton, characterized by distinctive 3,23-acetal/lactone-bridged functionalities. All isolated compounds were evaluated for their proangiogenic activities in transgenic zebrafish. Compound 3 exhibited significant proangiogenic activity, which notably increased the number and length of intersegmental blood vessels in model zebrafish in a dose-dependent manner at concentrations of 20 and 40 mu M. On a molecular scale, the tested compounds were modeled through molecular docking to have insight into the interactions with the possible target VEGFR2. Mechanistically, RT-qPCR results revealed that compound 3 could promote angiogenesis via activating VEGFR2 and subsequently activating the downstream PI3K/AKT and MAPK signaling pathways. These findings indicate that 3 could be a potential lead compound for developing angiogenesis agents.
资助项目	National Key R & D Pro-gram of China[2022YFC2804700] ; National Key R & D Pro-gram of China[2022YFC2804600] ; National Natural Science Foundation of China[42076090] ; National Natural Science Foundation of China[U2006203] ; Shandong Provincial Natural Science Foundation[ZR2021ZD28] ; Youth Innovation Promotion Association CAS[2023216] ; Senior User Project of the Research Vessel KEXUE of the National Major Science and Technology Infrastructure from the Chinese Academy of Sciences[KEXUE2020GZ02] ; RV KEXUE of the National Major Science and Technology Infrastructure from the Chinese Academy of Sciences ; Oceanographic Data Center at IOCAS
WOS关键词	IN-VIVO ; CYTOCHROME-P450 ; BIOSYNTHESIS ; ANGIOGENESIS
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:001153526300001
内容类型	期刊论文
源URL	[http://ir.qdio.ac.cn/handle/337002/184305]
专题	海洋研究所_实验海洋生物学重点实验室
通讯作者	Wang, Bin-Gui; Li, Xin
作者单位	1.Qilu Univ Technol, Engn Res Ctr Zebrafish Models Human Dis & Drug Scr, Shandong Prov Engn Lab Biol Testing Technol, Shandong Acad Sci,Biol Inst,Key Lab Biosensor Shan, Jingshi East Rd 28789, Jinan 250103, Peoples R China 2.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Biol & Biotechnol, Wenhai Rd 1, Qingdao 266237, Peoples R China 3.Chinese Acad Sci, Inst Oceanol, Ctr Ocean Mega Sci, CAS & Shandong Prov Key Lab Expt Marine Biol, Nanhai Rd 7, Qingdao 266071, Peoples R China 4.Univ Chinese Acad Sci, Yuquan Rd 19A, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Yan, Li-Hong,Li, Pei-Hai,Li, Xiao-Ming,et al. Bialorastins A-F, highly oxygenated and polycyclic andrastin-type meroterpenoids with proangiogenic activity from the deep-sea cold-seep-derived fungus Penicillium bialowiezense CS-283[J]. BIOORGANIC CHEMISTRY,2024,143:12.
APA	Yan, Li-Hong.,Li, Pei-Hai.,Li, Xiao-Ming.,Yang, Sui-Qun.,Liu, Ke-Chun.,...&Li, Xin.(2024).Bialorastins A-F, highly oxygenated and polycyclic andrastin-type meroterpenoids with proangiogenic activity from the deep-sea cold-seep-derived fungus Penicillium bialowiezense CS-283.BIOORGANIC CHEMISTRY,143,12.
MLA	Yan, Li-Hong,et al."Bialorastins A-F, highly oxygenated and polycyclic andrastin-type meroterpenoids with proangiogenic activity from the deep-sea cold-seep-derived fungus Penicillium bialowiezense CS-283".BIOORGANIC CHEMISTRY 143(2024):12.