Evaluation on the inhibition of pyrrol-2-yl ethanone derivatives to lactate dehydrogenase and anticancer activities.
Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. In order to develop bifunctional compounds as inhibitor of LDH-A and anticancer agents, two pyrrol-2-yl methanone (or ethanone) derivatives (PM1 and PM2) were synthesized and evaluated as inhibitors of LDH-A based on the enzyme assay and cell assay by spectroscopy analysis. Fluorescence and CD spectra results demonstrated that both the change of second structure of LDH-A and the affinity interaction for compounds to LDH-A gave great effect on the activity of LDH-A. In particular, low concentration of compounds (1μμ-25μμ) could change the level of pyruvate in cancer cells. Moreover, the in vitro assay results demonstrated that pyrrol-2-yl ethanone derivatives can inhibit the proliferation of cancer cells. Therefore, pyrrol-2-yl ethanone derivatives (PM2) can be both LDH-A inhibitor and anticancer agents.
School of Chemistry and Chemical engineering, Jiangsu University, Zhenjiang, 212013, PR China.
Na-Na
NN
Lu
School of Chemistry and Chemical engineering, Jiangsu University, Zhenjiang, 212013, PR China.
Zhao-Yue
ZY
Weng
School of Chemistry and Chemical engineering, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: chenqy@ujs.edu.cn.
Qiu-Yun
QY
Chen
School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
Daniel
D
Boison
School of Chemistry and Chemical engineering, Jiangsu University, Zhenjiang, 212013, PR China.
Xin-Xin
XX
Xiao
School of Pharmacy, Jiangsu University, Zhenjiang, 212013, PR China.
Jing
J
Gao
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000080864:Lactate Dehydrogenase 5; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000378:metabolism
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011758:Pyrroles; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5
Cancer; Inhibitor; Lactate dehydrogenase; Pyrrol-2-yl ethanone