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Novel Diketopiperazine Dihydroorotate Dehydrogenase Inhibitors Purified from Traditional Tibetan Animal Medicine Osteon Myospalacem Baileyi
Chemical Biology & Drug Design
Short Title: Chemical Biology & Drug Design
Format: Journal Article
Publication Year: 2015
Pages: 626 - 636
Sources ID: 93601
Notes: Accession Number: 109976420; 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; Affiliation:  1: Key Laboratory of Tibetan Medicine Research, Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining 810001, China  2: University of Chinese Academy of Sciences, Beijing 100039, China  3: University of Electronic Science and Technology of China, Chengdu 611731, China; Source Info: Oct2015, Vol. 86 Issue 4, p626; Subject Term: DIKETOPIPERAZINES; Subject Term: DIHYDROOROTATE dehydrogenase; Subject Term: TIBETAN medicine; Subject Term: DIPEPTIDES; Subject Term: MOLECULAR models; Subject Term: HYDROGEN bonding; Author-Supplied Keyword: cyclic dipeptides; Author-Supplied Keyword: Dihydroorotate dehydrogenase inhibitors; Author-Supplied Keyword: Osteon Myospalacem Baileyi; Author-Supplied Keyword: Tibetan medicine; Author-Supplied Keyword: two ‐ dimensional chromatography; Author-Supplied Keyword: two-dimensional chromatography; Number of Pages: 11p; Document Type: Article
Visibility: Public (group default)
Abstract: (Show)
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.