title: Synthesis and evaluation of benzylisoquinoline derivatives for their inhibition on pancreatic lipase and preadipocyte proliferation.
abstract: The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, (1)H NMR and (13)C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Hao-Yu
authors.initials: HY
authors.lastname: Lv
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Ji-Long
authors.initials: JL
authors.lastname: Zou
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Meng-Jun
authors.initials: MJ
authors.lastname: Duan
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Chu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: zhuliang17@gmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China. Electronic address: njjjq@aliyun.com.
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: Jiang
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D044182:Benzylisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008049:Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D044182:Benzylisoquinolines; D004791:Enzyme Inhibitors; D008049:Lipase; C518354:PNLIP protein, human
keywords: Adipocyte proliferation; Anti-obesity; Benzylisoquinoline alkaloid; Nelumbo nucifera; Pancreatic lipase inhibitor