Computer-aided discovery and biological characterization of human lactate dehydrogenase 5 inhibitors with anti-osteosarcoma activity.

Human lactate dehydrogenase 5 (hLDH5) is overexpressed in various tissues of human tumors, which could be a potential therapeutic target for cancer treatment. Herein, we describe the computer-aided discovery and biological characterizations of hLDH5 inhibitors with anti-osteosarcoma activity. Biochemical assay indicated that the identified compounds 3 and 9 strongly inhibited hLDH5 function with EC values of 0.67 and 0.39 µM, respectively. The MTT assay revealed that most of the identified inhibitors had little effect on MG-63 cell proliferation at 4 µM, only 9 reduced the cancer cell proliferation at the same concentration, with an IC value of 3.18 µM. Our data suggested that 9 could be a starting lead of developing potent hLDH5 inhibitor for the anti-osteosarcoma agents in cancer treatment.