title: Structure-based drug design using GPCR homology modeling: toward the discovery of novel selective CysLT2 antagonists.
abstract: 3D structure of CysLT2 receptor was constructed by using homology modeling and molecular simulations. The binding pocket of CysLT2 receptor and the proposition of the interaction mode between CysLT2 and HAMI3379 were identified. A series of dicarboxylated chalcones was then virtually evaluated through molecular docking studies. A total of six compounds 13a-f with preferable scores was further synthesized and tested for CysLT2 antagonistic activities by determination of the cytosolic free Ca(2+) levels in HEK293 cells. Compounds 13e and 13f exhibited potent and selective CysLT2 antagonistic activities with IC50 values being 7.5 and 0.25 μM, respectively.
authors: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Xiaowu
authors: X
authors: Dong
authors: Yanmei
authors: Y
authors: Zhao
authors: Xueqin
authors: X
authors: Huang
authors: Kana
authors: K
authors: Lin
authors: Jianzhong
authors: J
authors: Chen
authors: Erqing
authors: E
authors: Wei
authors: Tao
authors: T
authors: Liu
authors: Yongzhou
authors: Y
authors: Hu
mesh_terms: D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D018077:Receptors, Leukotriene / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D018077:Receptors, Leukotriene; C412375:cysteinyl leukotriene receptor 2