The Anti-inflammatory Activiy of Metal Complexes of Heterocyclic Thiosemicarbazones, 2-Substituted Pyridine N-Oxides and 2-Pyridylthioureas
Corresponding Author
Iris H. Hall
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USA
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USASearch for more papers by this authorS. Y. Chen
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USA
Search for more papers by this authorK. G. Rajendran
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USA
Search for more papers by this authorD. X. West
Department of Chemistry, Illinois State University, Norman, IL 61790–4160, USA
Search for more papers by this authorCorresponding Author
Iris H. Hall
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USA
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USASearch for more papers by this authorS. Y. Chen
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USA
Search for more papers by this authorK. G. Rajendran
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, CB 7360, University of North Carolina, Chapel Hill, NC 27599, USA
Search for more papers by this authorD. X. West
Department of Chemistry, Illinois State University, Norman, IL 61790–4160, USA
Search for more papers by this authorAbstract
The thiosemicarbazones and their related metal complexes were shown to be potent anti-inflammatory agents in rodents at 8 mg kg−1. They were effective in blocking induced edema and endotoxic shock while blocking both local and central pain processes. The ability of the agents to function as anti-inflammatory agents is multifold. First, Tumor Necrosis Factor-alpha (TNFα) and Interleukin-1 (IL-1) release was markedly reduced by the agents. Second, high-affinity receptor binding on fibroblasts of TNFα and IL-1 was significantly inhibited. Third, cellular events, e.g. lysosomal enzymes of specific cells, such as macrophages, were inhibited and prostaglandin cyclo-oxygenase and leukotriene 5′-lipoxygenase enzymic synthetic rates were significantly reduced, which should cause an overall reduction of the inflammatory process.
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