Discovery of human lactate dehydrogenase A (LDHA) inhibitors as anticancer agents to inhibit the proliferation of MG-63 osteosarcoma cells

MedChemComm
2017.0

Abstract

Human lactate dehydrogenase A (LDHA) has been identified as a potential therapeutic target in the area of cancer metabolism. Herein, we report the discovery of novel LDHA inhibitors through docking-based virtual screening and biological assays. The primary enzymatic assay suggested that compound <b>11</b> targeted LDHA with an IC<sub>50</sub> value of 0.33 μM. The <i>in vitro</i> cytotoxic assay demonstrated that compound <b>11</b> reduced the growth of MG-63 cancer cells with an EC<sub>50</sub> value of 3.35 μM. Finally, we found that compound <b>11</b> induced the apoptosis of MG-63 cancer cells in a dose dependent manner, upregulated the oxygen consumption rate (OCR), and decreased the lactate formation and extracellular acidification rate (ECAR) in MG-63 cancer cells. Collectively, our data suggested that compound <b>11</b> could be a promising lead for the development of potent LDHA inhibitors.

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