干旱区生态环境知识资源中心(Arid): Design, synthesis and screening of a drug discovery library based on an Eremophila-derived serrulatane scaffold

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DOI	10.1016/j.phytochem.2021.112887
	Design, synthesis and screening of a drug discovery library based on an Eremophila-derived serrulatane scaffold
	Zhang, Chen; Lum, Kah Yean; Taki, Aya C.; Gasser, Robin B.; Byrne, Joseph J.; Wang, Tao; Blaskovich, Mark A. T.; Register, Emery T.; Montaner, Luis J.; Tietjen, Ian; Davis, Rohan A.
通讯作者	Davis, RA (corresponding author), Griffith Univ, Sch Environm & Sci, Griffith Inst Drug Discovery, Brisbane, Qld 4111, Australia.
来源期刊	PHYTOCHEMISTRY
ISSN	0031-9422
EISSN	1873-3700
出版年	2021
卷号	190
英文摘要	Chemical studies of the aerial parts of the Australian desert plant Eremophila microtheca afforded the targeted and known diterpenoid scaffolds, 3,7,8-trihydroxyserrulat-14-en-19-oic acid and 3-acetoxy-7,8-dihydroxyserrulat14-en-19-oic acid. The most abundant serrulatane scaffold was converted to the poly-methyl derivatives, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester and 3,7,8-trimethoxyserrulat-14-en-19-oic acid methyl ester using simple and rapid methylation conditions consisting of DMSO, NaOH and MeI at room temperature. Subsequently a 12-membered amide library was synthesised by reacting the methylated scaffolds with a diverse series of commercial primary amines. The chemical structures of the 12 undescribed semi-synthetic analogues were fully characterised following 1D/2D NMR, MS, UV, ECD and [alpha](D) data analyses. All compounds were evaluated for their anthelmintic, anti-microbial and anti-viral activities. While none of the compounds significantly inhibited motility or development of the exsheathed third-stage larvae (xL3s) of a pathogenic ruminant parasite, Haemonchus contortus, the tri-methylated analogue induced a skinny phenotype in fourth-stage larvae (L4s) after seven days of treatment (IC50 = 14 mu M). Anti-bacterial and anti-fungal activities were not observed at concentrations up to 20 mu M. Activity against HIV latency reversal was tested in inducible, chronically-infected cells, with the tri-methylated analogue being the most active (EC50 = 38 mu M).
英文关键词	Eremophila microtheca Scrophulariaceae Serrulatane Scaffold Amide Methylation Semi-synthesis Anthelmintic Haemonchus contortus Anti-bacterial Anti-fungal Anti-HIV
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000687318400008
WOS关键词	AMIDE BOND FORMATION ; ANTIBACTERIAL CONSTITUENTS ; FREDERICAMYCIN-A ; ANALOGS ; LEUBETHANOL ; DERIVATIVES ; DITERPENES
WOS类目	Biochemistry & Molecular Biology ; Plant Sciences
WOS研究方向	Biochemistry & Molecular Biology ; Plant Sciences
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/364319
作者单位	[Zhang, Chen; Lum, Kah Yean; Davis, Rohan A.] Griffith Univ, Sch Environm & Sci, Griffith Inst Drug Discovery, Brisbane, Qld 4111, Australia; [Taki, Aya C.; Gasser, Robin B.; Byrne, Joseph J.; Wang, Tao] Univ Melbourne, Fac Vet & Agr Sci, Melbourne Vet Sch, Dept Vet Biosci, Parkville, Vic 3010, Australia; [Blaskovich, Mark A. T.] Univ Queensland, Inst Mol Biosci, Ctr Superbug Solut, Community Open Antimicrobial Drug Discovery, Brisbane, Qld 4072, Australia; [Register, Emery T.; Montaner, Luis J.; Tietjen, Ian] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA
推荐引用方式 GB/T 7714	Zhang, Chen,Lum, Kah Yean,Taki, Aya C.,et al. Design, synthesis and screening of a drug discovery library based on an Eremophila-derived serrulatane scaffold[J],2021,190.
APA	Zhang, Chen.,Lum, Kah Yean.,Taki, Aya C..,Gasser, Robin B..,Byrne, Joseph J..,...&Davis, Rohan A..(2021).Design, synthesis and screening of a drug discovery library based on an Eremophila-derived serrulatane scaffold.PHYTOCHEMISTRY,190.
MLA	Zhang, Chen,et al."Design, synthesis and screening of a drug discovery library based on an Eremophila-derived serrulatane scaffold".PHYTOCHEMISTRY 190(2021).