Synthesis and pharmacological evaluation of novel derivatives of anti-inflammatory drugs with increased antioxidant and anti-inflammatory activities

Abstract

The role of reactive oxygen species in inflammatory processes has been well documented, while several antioxidant compounds have been shown to exhibit anti‐inflammatory activity. We designed novel compounds as potential agents that combine enhanced antioxidant and anti‐inflammatory activities. Derivatives of indomethacin, diclofenac, tolfenamic acid, and ibuprofen, four widely used nonsteroidal anti‐inflammatory drugs, with cysteamine, a polar antioxidant molecule, were synthesized. The compounds were evaluated for their effect on free radical processes (protection against rat hepatic microsomal lipid‐peroxidation and interaction with the stable free radical 1,1‐diphenyl‐2‐picrylhydrazyl), as well as on carrageenan‐induced inflammation (mouse paw edema inhibition). Furthermore, ulcerogenicity tests in rats were performed in order to evaluate the gastrointestinal irritation of the novel indomentacin derivative. It was found that all compounds were very potent antioxidants in vitro; they could inhibit lipid peroxidation very significantly, having IC50 values ranging from 55 to 510 μM, while they could also interact ∼90% with DPPH at equimolar concentrations. We attribute these activities to their sulfhydryl group, as well as to their increased lipophilicity compared to cysteamine. Furthermore, the derivatives demonstrated significant anti‐inflammatory activity, comparable to that of the parent molecules, while they showed significantly reduced ulcerogenic potency. Our results indicate that the combined pharmacological properties of these new derivatives may prove useful for the design and development of novel cytoprotective/anti‐inflammatory molecules with potentially important therapeutic applications. Drug Dev. Res. 47:9–16, 1999. © 1999 Wiley‐Liss, Inc.

Alkannin and Shikonin: Effect on Free Radical Processes and on Inflammation - A Preliminary Pharmacochemical Investigation

“…(e.g. wound healing, antiinflammatory) free radical processes and oxidative stress are implicated [9,10,11]. Their hydroxyquinone structure suggests involvement of these compounds in free radical processes.…”

Screening of antioxidant activity of lichens Parmotrema reticulatum and Usnea sp. from Darjeeling hills, India

“…ROS are various forms of activated oxygen, which include free radicals such as superoxide anion radicals (O -2 ) and hydroxyl radicals (OH -1 ), as well as non-free radical species (H 2 O 2 ) and the singlet oxygen ( 1 O 2 )[1, 2,3,4]. Also, excessive generation of ROS, induced by various stimuli and which exceed the antioxidant capacity of the organism, leads to a variety of pathophysiological processes such as inflammation, diabetes, genotoxicity, and cancer [5,6,7]. Exogenous sources of free radicals include tobacco smoke, ionizing radiation, certain pollutants, organic solvents, and pesticides [3,8,9,10].…”

In vitro anti-oxidant activity of the leaves of Dillenia indica

“…In recent years, oxygenderived free radicals have been reported to be closely involved in many biological symptoms such as inflammation, cancer, atherosclerosis, and coronary heart disease (Kourounakis et al, 1999;Gulcin et al, 2002). To prevent or delay the oxidation process, addition of antioxidants to foods is the most extensively used method.…”