Novel Diketopiperazine Dihydroorotate Dehydrogenase Inhibitors Purified from Traditional Tibetan Animal Medicine Osteon Myospalacem Baileyi

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	Novel Diketopiperazine Dihydroorotate Dehydrogenase Inhibitors Purified from Traditional Tibetan Animal Medicine Osteon Myospalacem Baileyi
	Jiang, Lei 1,2; Wen, Huaixiu 1,2; Shao, Yun 1; Yu, Ruitao 1; Liu, Zenggen 1; Wang, Shuo 1,2; Wang, Qilan 1; Zhao, Xiaohui 1; Zhang, Peng 3; Tao, Yanduo 1; Mei, Lijuan 1
	2015-10-01
发表期刊	CHEMICAL BIOLOGY & DRUG DESIGN
卷号	86 期号:4 页码:626-636
文章类型	Article
摘要	Traditional Tibetan medicine provides an abundant source of knowledge on human ailments and their treatment. As such, it is necessary to explore their active single compounds used to treat these ailments to discover lead compounds with good pharmacologic properties. In this present work, animal medicine, Osteon Myospalacem Baileyi extracts have been separated using a two-dimensional preparative chromatographic method to obtain single compounds with high purity as part of the following pharmacological research. Five high-purity cyclic dipeptides from chromatography work were studied for their dihydroorotate dehydrogenase inhibitory activity on recombinant human dihydroorotate dehydrogenase enzyme and compound Fr. 1-4 was found to contain satisfying inhibition activity. The molecular modeling study suggests that the active compound Fr. 1-4 may have a teriflunomide-like binding mode. Then, the energy decomposition study suggests that the hydrogen bond between Fr. 1-4 and Arg136 can improve the binding mode to indirectly increase the van der Waals binding energy. All the results above together come to the conclusion that the 2, 5-diketopiperazine structure group can interact with the polar residues well in the active pocket using electrostatic power. If some proper hydrophobic groups can be added to the sides of the 2, 5-diketopiperazine group, it is believed that better 2, 5-diketopiperazine dihydroorotate dehydrogenase inhibitors will be found in the future.; Traditional Tibetan medicine provides an abundant source of knowledge on human ailments and their treatment. As such, it is necessary to explore their active single compounds used to treat these ailments to discover lead compounds with good pharmacologic properties. In this present work, animal medicine, Osteon Myospalacem Baileyi extracts have been separated using a two-dimensional preparative chromatographic method to obtain single compounds with high purity as part of the following pharmacological research. Five high-purity cyclic dipeptides from chromatography work were studied for their dihydroorotate dehydrogenase inhibitory activity on recombinant human dihydroorotate dehydrogenase enzyme and compound Fr. 1-4 was found to contain satisfying inhibition activity. The molecular modeling study suggests that the active compound Fr. 1-4 may have a teriflunomide-like binding mode. Then, the energy decomposition study suggests that the hydrogen bond between Fr. 1-4 and Arg136 can improve the binding mode to indirectly increase the van der Waals binding energy. All the results above together come to the conclusion that the 2, 5-diketopiperazine structure group can interact with the polar residues well in the active pocket using electrostatic power. If some proper hydrophobic groups can be added to the sides of the 2, 5-diketopiperazine group, it is believed that better 2, 5-diketopiperazine dihydroorotate dehydrogenase inhibitors will be found in the future.
关键词	Cyclic Dipeptides Dihydroorotate Dehydrogenase Inhibitors Osteon Myospalacem Baileyi Tibetan Medicine Two-dimensional Chromatography
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]	REVERSED-PHASE SEPARATIONS ; PLASMODIUM-FALCIPARUM ; DRUG ; BIOSYNTHESIS ; PATHWAY ; SODIUM ; LIQUID
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal
WOS记录号	WOS:000362163500026
引用统计	被引频次：4[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/5501
专题	中国科学院西北高原生物研究所
作者单位	1.Chinese Acad Sci, Northwest Plateau Inst Biol, Key Lab Tibetan Med Res, Xining 810001, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100039, Peoples R China 3.Univ Elect Sci & Technol China, Chengdu 611731, Peoples R China
推荐引用方式 GB/T 7714	Jiang, Lei,Wen, Huaixiu,Shao, Yun,et al. Novel Diketopiperazine Dihydroorotate Dehydrogenase Inhibitors Purified from Traditional Tibetan Animal Medicine Osteon Myospalacem Baileyi[J]. CHEMICAL BIOLOGY & DRUG DESIGN,2015,86(4):626-636.
APA	Jiang, Lei.,Wen, Huaixiu.,Shao, Yun.,Yu, Ruitao.,Liu, Zenggen.,...&Mei, Lijuan.(2015).Novel Diketopiperazine Dihydroorotate Dehydrogenase Inhibitors Purified from Traditional Tibetan Animal Medicine Osteon Myospalacem Baileyi.CHEMICAL BIOLOGY & DRUG DESIGN,86(4),626-636.
MLA	Jiang, Lei,et al."Novel Diketopiperazine Dihydroorotate Dehydrogenase Inhibitors Purified from Traditional Tibetan Animal Medicine Osteon Myospalacem Baileyi".CHEMICAL BIOLOGY & DRUG DESIGN 86.4(2015):626-636.

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