title: Synthesis and antitumor activity of 1,3,4-oxadiazole possessing 1,4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors.
abstract: A series of 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (7a-7q) have been designed, synthesized and evaluated for their antitumor activity. Most of the synthesized compounds were proved to have potent antitumor activity and low toxicity. Among them, compound 7a showed the most potent biological activity against Human Umbilical Vein Endothelial cells, which was comparable to the positive control. The results of apoptosis and flow cytometry (FCM) demonstrated that compound 7a induce cell apoptosis by the inhibition of MetAP2 pathway. Molecular docking was performed to position compound 7a into MetAP2 binding site in order to explore the potential target.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Sun
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Li
authors.forename: Shao-Song
authors.initials: SS
authors.lastname: Qian
authors.forename: Feng-Jiao
authors.initials: FJ
authors.lastname: Guo
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Dang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Ya-Rong
authors.initials: YR
authors.lastname: Xue
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004146:Dioxanes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology; D006801:Humans; D063208:Methionyl Aminopeptidases; D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004146:Dioxanes; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D010069:Oxadiazoles; D011480:Protease Inhibitors; C583463:1,3,4-oxadiazole; D000626:Aminopeptidases; C081311:METAP2 protein, human; D063208:Methionyl Aminopeptidases; C527681:1,4-benzodioxan