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Combined Structure-Based Pharmacophore and 3D-QSAR Studies on Phenylalanine Series Compounds as TPH1 Inhibitors
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China
State Key Laboratory Breeding Base of Systematic research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610041, China
* Authors to whom correspondence should be addressed.
Received: 2 February 2012; in revised form: 13 April 2012 / Accepted: 25 April 2012 / Published: 2 May 2012
Abstract: Tryptophan hydroxylase-1 (TPH1) is a key enzyme in the synthesis of serotonin. As a neurotransmitter, serotonin plays important physiological roles both peripherally and centrally. In this study, a combination of ligand-based and structure-based methods is used to clarify the essential quantitative structure-activity relationship (QSAR) of known TPH1 inhibitors. A multicomplex-based pharmacophore (MCBP) guided method has been suggested to generate a comprehensive pharmacophore of TPH1 kinase based on three crystal structures of TPH1-inhibitor complex. This model has been successfully used to identify the bioactive conformation and align 32 structurally diverse substituted phenylalanine derivatives. The QSAR analyses have been performed on these TPH1 inhibitors based on the MCBP guided alignment. These results may provide important information for further design and virtual screening of novel TPH1 inhibitors.
Keywords: pharmacophore; 3D-QSAR; tryptophan hydroxylase; inhibitors
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MDPI and ACS Style
Ouyang, L.; He, G.; Huang, W.; Song, X.; Wu, F.; Xiang, M. Combined Structure-Based Pharmacophore and 3D-QSAR Studies on Phenylalanine Series Compounds as TPH1 Inhibitors. Int. J. Mol. Sci. 2012, 13, 5348-5363.
Ouyang L, He G, Huang W, Song X, Wu F, Xiang M. Combined Structure-Based Pharmacophore and 3D-QSAR Studies on Phenylalanine Series Compounds as TPH1 Inhibitors. International Journal of Molecular Sciences. 2012; 13(5):5348-5363.
Ouyang, Liang; He, Gu; Huang, Wei; Song, Xiangrong; Wu, Fengbo; Xiang, Mingli. 2012. "Combined Structure-Based Pharmacophore and 3D-QSAR Studies on Phenylalanine Series Compounds as TPH1 Inhibitors." Int. J. Mol. Sci. 13, no. 5: 5348-5363.