title: Synthesis, biological evaluation and molecular docking studies of 1,3,4-oxadiazole derivatives as potential immunosuppressive agents.
abstract: A series of 1,3,4-oxadiazole derivatives derived from 4-methoxysalicylic acid or 4-methylsalicylic acid (6a-6z) have been first synthesized for their potential immunosuppressive activity. Among them, compound 6z displayed the most potent biological activity against lymph node cells (inhibition=38.76% for lymph node cells and IC(50)=0.31 μM for PI3Kγ). The preliminary mechanism of compound 6z inhibition effects was also detected by flow cytometry (FCM) and the compound exerted immunosuppressive activity via inducing the apoptosis of activated lymph node cells in a dose dependent manner. Docking simulation was performed to position compound 6z into the PI3Kγ structure active site to determine the probable binding model.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Zhang
authors.forename: Zong-Zheng
authors.initials: ZZ
authors.lastname: Zhao
authors.forename: Ru
authors.initials: R
authors.lastname: Yan
authors.forename: Rui
authors.initials: R
authors.lastname: Xu
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Gong
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020134:Catalytic Domain; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D010069:Oxadiazoles