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 11 targeted LDHA with an IC₅₀ value of 0.33 μM. The in vitro cytotoxic assay demonstrated that compound 11 reduced the growth of MG-63 cancer cells with an EC₅₀ value of 3.35 μM. Finally, we found that compound 11 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 11 could be a promising lead for the development of potent LDHA inhibitors.

中文翻译：

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发现人乳酸脱氢酶A（LDHA）抑制剂作为抑制MG-63骨肉瘤细胞增殖的抗癌剂

人乳酸脱氢酶A（LDHA）已被确定为癌症代谢领域的潜在治疗靶标。在这里，我们报告通过基于对接的虚拟筛选和生物学分析发现新型LDHA抑制剂。初级酶分析表明，化合物11靶向LDHA的IC ₅₀值为0.33μM 。在体外细胞毒性试验表明，化合物11降低MG-63的癌细胞的生长与EC ₅₀ 3.35μM的值。最后，我们发现化合物11剂量依赖性地诱导MG-63癌细胞的凋亡，上调耗氧率（OCR），降低MG-63癌细胞的乳酸形成和细胞外酸化率（ECAR）。总体而言，我们的数据表明化合物11可能是有效LDHA抑制剂开发的有希望的先导。