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

• DOI: 10.1111/cbdd.12530
• Publication Date: 2015-01-28T07:54:48Z
• Authors: Lei Jiang; Huaixiu Wen; Yun Shao; Ruitao Yu; Zenggen Liu; Shuo Wang; Qilan Wang; Xiaohui Zhao; Peng Zhang; Yanduo Tao; Lijuan Mei
• Keywords: Dihydroorotate Dehydrogenase

Traditional Tibetan medicine provides an abundant source of knowledge on human ailments and their treatment. As such, it is necessary to explore active single compounds used treat these discover lead with good pharmacologic properties. In this present work, animal medicine, Osteon Myospalacem Baileyi extracts have been separated using a two‐dimensional preparative chromatographic method obtain high purity as part the following pharmacological research. Five high‐purity cyclic dipeptides from chromatography work were studied for dihydroorotate dehydrogenase inhibitory activity recombinant enzyme compound Fr. 1‐4 was found contain satisfying inhibition activity. The molecular modeling study suggests that may teriflunomide‐like binding mode. Then, energy decomposition hydrogen bond between Arg136 can improve mode indirectly increase van der Waals energy. All results above together come conclusion 2, 5‐diketopiperazine structure group interact polar residues well in pocket electrostatic power. If some proper hydrophobic groups be added sides group, believed better inhibitors will future.