Phenothiazines as lipid peroxidation inhibitors and cytoprotective agents. 1992

M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.

A series of phenothiazines was synthesized and evaluated as in vitro inhibitors of iron-dependent lipid peroxidation. The MIC (minimum tested concentration that gave greater than or equal to 50% inhibition) for 2-(10H-phenothiazin-2-yloxy)-N,N-dimethylethanolamine methanesulfonate (6) was 0.26 microM. Whereas methyl substitution at N-10 diminished activity nearly 100-fold, other structural modifications such as varying the amine group, the distance separating the amine substituent from the phenothiazine nucleus, and the linking group had little effect. Compound 6 was more effective than probucol, a known antioxidant, in blocking Cu2+ catalyzed oxidation of low-density lipoprotein (LDL) as measured by competitive scavenger receptor mediated degradation of 125I-labeled acetyl-LDL by mouse peritoneal macrophage cells in vitro. At a concentration of 5 microM, compound 6 also protected primary cultures of rat hippocampal neurons exposed to hydrogen peroxide (50 microM) when assessed 18 h later by fluorescein diacetate and propidium iodide uptake.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008563 Membrane Lipids Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. Cell Membrane Lipid,Cell Membrane Lipids,Membrane Lipid,Lipid, Cell Membrane,Lipid, Membrane,Lipids, Cell Membrane,Lipids, Membrane,Membrane Lipid, Cell,Membrane Lipids, Cell
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D010529 Peritoneal Cavity The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the STOMACH. The two sacs are connected by the foramen of Winslow, or epiploic foramen. Greater Sac,Lesser Sac,Omental Bursa,Bursa, Omental,Cavity, Peritoneal,Sac, Greater,Sac, Lesser
D010640 Phenothiazines Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon

Related Publications

M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
January 1985, Vestnik Akademii meditsinskikh nauk SSSR,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
July 1966, Lipids,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
December 1994, The Journal of pharmacy and pharmacology,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
December 1999, Neurotoxicity research,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
September 2003, Chemistry and physics of lipids,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
June 1983, Biochemical Society transactions,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
January 1987, Chemistry and physics of lipids,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
July 1994, Die Pharmazie,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
January 1998, Advances in experimental medicine and biology,
M J Yu, and J R McCowan, and K J Thrasher, and P T Keith, and C A Luttman, and P P Ho, and R D Towner, and B Bertsch, and J S Horng, and S L Um
May 1985, Methods and findings in experimental and clinical pharmacology,
Copied contents to your clipboard!