title: Discovery of 2-((3-cyanopyridin-2-yl)thio)acetamides as human lactate dehydrogenase A inhibitors to reduce the growth of MG-63 osteosarcoma cells: Virtual screening and biological validation.
abstract: Lactate dehydrogenase A (LDHA) has emerged as an attractive target in the oncology field. In this paper, we present the identification of 2-((3-cyanopyridin-2-yl)thio)acetamide-containing compounds as LDHA inhibitors. The in vitro enzymatic assay suggested that inhibitor 9 had good inhibitory potency against LDHA with IC50 value as 1.24μM. Cytotoxicity assay showed that inhibitor 9 strongly inhibited the proliferation of cancer cell MG-63 (EC50=0.98μM). These findings indicated that inhibitor 9 could be employed as a lead for developing more potent LDHA inhibitor with anti-proliferative potency.
authors.affiliation: Department of Orthopedics, Heilongjiang Province Hospital, Harbin 150036, Heilongjiang Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Orthopedics, Heilongjiang Province Hospital, Harbin 150036, Heilongjiang Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Orthopedics, Heilongjiang Province Hospital, Harbin 150036, Heilongjiang Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Orthopedics, Heilongjiang Province Hospital, Harbin 150036, Heilongjiang Province, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, Heilongjiang Province Hospital, Harbin 150036, Heilongjiang Province, China.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Harbin Medical University Cancer Hospital, Harbin 150081, Heilongjiang Province, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Traditional Chinese Medicine Hospital of Harbin, Harbin 150000, Heilongjiang Province, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Affiliated Hospital of Putian University, Putian 351100, Fujian Province, China. Electronic address: xuanhuang_chen@163.com.
authors.forename: Xuanhuang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D062105:Molecular Docking Simulation; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry
chemical_list: D000081:Acetamides; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011725:Pyridines; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C023666:pyridine
keywords: Apoptosis; Cytotoxic assay; Lactate dehydrogenase A; Virtual screening