N. R. Mikusic, M. Rosón, S. D. Penna
2016
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Influential Citations
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Quality indicators
Journal
Anti-inflammatory & anti-allergy agents in medicinal chemistry
Abstract
BACKGROUND Designing new anti-inflammatory agents possessing safe therapeutic profiles and devoid of potential undesirable side effects is an active field in medicinal chemistry. Thus, a series of N-(4-substituted phenyl)glycine derivatives was designed and synthesized. The idea behind the design is to utilize the bifunctionality of 4-aminoacetophenone via converting the amino group into glycine derivative as a side arm to mimic the glycine amino acid enhancing the overall physicochemical and biological characteristics. In addition, the opposite acetyl group was used as a center for modification and derivatization. METHODS The starting N-(4-acetylphenyl)glycine was converted into two intermediates: the chalcone analog 2 and the thiosemicarbazone derivative 8. Both 2 and 8 were derivatized and/or cyclized into different heterocyclic target derivatives (3-7 and 9-12). The target compounds were screened for anti-inflammatory activity using carrageenan-induced rat paw edema assay. RESULTS The results showed that compounds 6, 7, and 3, were the most active among the tested compounds at 50 mg/kg dose level with % inhibition of edema of 51.82, 43.80, and 40.39, respectively. CONCLUSION The authors succeeded to introduce a simple and versatile skeleton with a side arm resembling the glycine amino acid; imparting a potential improvement in physicochemical properties. We utilize the other side of the skeleton's aromatic ring as a center for derivatization. The chalcone analog and its cyclized heterocyclic derivatives were of remarkably higher anti-inflammatory activity than the thiosemicarbazone and its derivatives.