Synthesis, cytotoxicity for mimics of catalase: Inhibitors of lactate dehydrogenase and hypoxia inducible factor

• Pyrrol-conjugated CO groups can increase the activity of Mn complex to LDH-A.
• The Mn complexes were firstly found to be inhibitor of LDH-A and HIF-1α.
• Mn(II) complexes exhibit high cytotoxicity to HepG-2 cells.
• A chemical sensitizer to explore HIF-1α related oxygen and energy metabolism is suggested.

Lactate dehydrogenase A (LDH-A) is a potentially important metabolic target for the inhibition of the highly activated glycolysis pathway in cancer cells. Two Mn(II) complexes with ligand containing di(pyridylmethyl) amine and pyrrol-ketone were used to attenuate the activity of LDH-A. The inhibition of the manganese(II) complexes on the proliferation of HepG-2 cells is related to their ability to disproportionate H2O2. Importantly, the synthesized mimic of catalase can decrease the expression of hypoxia inducible factor (HIF-1α) in HepG-2 cells. So we envision that the multifunctional mimics of catalase could attenuate the activity of LDH-A signaling the cancer cells to death through HIF-1α involved path.

Special Mn(II) complexes were used firstly as inhibitor of LDH-A to attenuate the proliferation of cancer cells and the expression of HIF-1α.Figure optionsDownload as PowerPoint slide