Glyoxalase inhibitors as potential anticancer agents.
06 Jun 1969-Biochemical and Biophysical Research Communications (Academic Press)-Vol. 35, Iss: 5, pp 593-598
TL;DR: A study of a series of S-alkylglutathiones as inhibitors of the enzyme, glyoxalase I, revealed that a non-polar region exists on the enzyme which plays an important role in the formation of an enzyme-inhibitor complex.
About: This article is published in Biochemical and Biophysical Research Communications.The article was published on 1969-06-06. It has received 105 citations till now. The article focuses on the topics: Lactoylglutathione lyase & Glutathione.
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TL;DR: This comprehensive review summarizes fundamental principles of glutathione catalysis and compares the structures and mechanisms ofglutathione-dependent enzymes, including glutathion reductase, glutaredoxins, glutATHione peroxidases, peroxiredoxinases, glyoxalases 1 and 2, glutthione transferases and MAPEG.
814 citations
Cites background from "Glyoxalase inhibitors as potential ..."
...In 1969, Vince and Ward then proposed to directly inhibit Glo1 to cause a build-up of endogenous MG in order to kill cancer cells [436]....
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TL;DR: The modification of nucleic acids and protein by methylglyoxal is a signal for their degradation and may have a role in the development of diabetic complications, atherosclerosis, the immune response in starvation, aging and oxidative stress.
Abstract: 1. Methylglyoxal is a reactive alpha-oxoaldehyde and physiological metabolite formed by the fragmentation of triose-phosphates, and by the metabolism of acetone and aminoacetone. 2. Methylglyoxal modifies guanylate residues to form 6,7-dihydro-6,7-dihydroxy-6-methyl-imidazo[2,3-b]purine-9(8)one and N2-(1-carboxyethyl)guanylate residues and induces apoptosis. 3. Methylglyoxal modifies arginine residues in proteins to form N(delta)-(4,5-dihydroxy-4-methylimidazolidin-2-yl) ornithine, N(delta)-(5-hydro-5-methylimidazol-4-on-2-yl)ornithine and N(delta)-(5)methylimidazol-4-on-2-yl)ornithine residues. 4. Methylglyoxal-modified proteins undergo receptor-mediated endocytosis and lysosomal degradation in monocytes and macrophages, and induce cytokine synthesis and secretion. 5. Methylglyoxal is detoxified by the glyoxalase system. Decreased detoxification of methylglyoxal may be induced pharmacologically by glyoxalase I inhibitors which have anti-tumor and anti-malarial activities. 6. The modification of nucleic acids and protein by methylglyoxal is a signal for their degradation and may have a role in the development of diabetic complications, atherosclerosis, the immune response in starvation, aging and oxidative stress.
568 citations
495 citations
TL;DR: A comprehensive overview of methylglyoxal research, extending discussion from chemistry to biological implications by reviewing some important characteristics of methyl glyoxal metabolism and toxicity in a wide variety of species, and emphasizing the action of methyl-oxoaldehyde production in the environment as a potential risk factor and to the possible role of this a-dicarbonyl in diseases as discussed by the authors.
483 citations
TL;DR: The glyoxalase system is a metabolic pathway that catalyses the detoxification of alpha-oxoaldehydes RCOCHO to corresponding aldonic acids RCH(OH)CO2H, and protects cells from alpha-Oxoaldehyde-mediated formation of advanced glycation endproducts (AGEs).
306 citations
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TL;DR: On the basis of the assumed theory the rate of the observed reaction is directly proportional to the concentration of the enzyme-substrate compound, where (E:l = (ES).
Abstract: On the basis of the assumed theory the rate of the observed reaction is directly proportional to the concentration of the enzyme-substrate compound, (ES), a t all values of the concentration of the substrate, (S). It is proportional to (S) only a t low values of (S). The numerical value of the dissociation constant is given by the substrate concentration a t half-maximum velocity, where (E:l = (ES). The equilibrium in equation 1 may be heterogeneous or homogeneous. Hitchcock'\" has pointed
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Journal Article•
TL;DR: 3-Ethoxy-2-ketobutyraldehyde (Kethoxal®) increases, consistently, the life span of mice with Leukemia L1210 and shows some antileukemic activity.
Abstract: Summary 1.3-Ethoxy-2-ketobutyraldehyde (Kethoxal®) increases, consistently, the life span of mice with Leukemia L1210. 2.Phenylglyoxal, cyclohexylglyoxal, methoxy-methylglyoxal, glyoxal, succinaldehyde, and malonaldehyde also showed some antileukemic activity. 3.Relationships among structure, activity, and side effects are discussed.
70 citations