Synthesis, cytotoxicity for mimics of catalase: inhibitors of lactate dehydrogenase and hypoxia inducible factor.
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.
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
Juan-Juan
JJ
Xue
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China. Electronic address: chenqy@ujs.edu.cn.
Qiu-Yun
QY
Chen
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
Meng-Yun
MY
Kong
School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.
Chun-Yin
CY
Zhu
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, PR China.
Zhi-Rong
ZR
Gen
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, PR China.
Zhi-Lin
ZL
Wang
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism*; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors*; D000080864:Lactate Dehydrogenase 5; D008024:Ligands; D008345:Manganese / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D008024:Ligands; D009942:Organometallic Compounds; D011758:Pyrroles; D008345:Manganese; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D002374:Catalase
Cancer cells; HIF; LDH; Manganese; Mimics of catalase