Skip to content
2000
Volume 18, Issue 9
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background: Over the years, the xanthone nucleus has been serving as an interesting scaffold for the design of derivatives aiming at anti-inflammatory drug development. Objective: The objective of the current work was to design and synthesize two series of novel 3- (5'-substituted pentyloxy)-1-hydroxy xanthone & 6-(5'-substituted pentyloxy)-1-hydroxy xanthone derivatives. The designed compounds were examined in vivo for anti-inflammatory activity. The effect of the synthesized xanthone derivatives on the serum expression of IL-10 and TNF-α was evaluated to understand the underlying molecular mechanisms. Methods: The title compounds were virtually designed and screened for ADME/T properties and docked onto the COX-2 protein. The synthesis of the xanthone derivatives was achieved by the condensation of salicylic acid derivatives and a suitable phenol in the presence of a mixture of phosphorus pentoxide–methanesulfonic acid as an acylation catalyst. The compounds were evaluated for in vivo anti-inflammatory activity by carrageenan induced paw edema method and serum expression of cytokines was evaluated using ELISA assays. Results: The selected compounds exhibited docking scores ranging between -10.7 to -6.8 (Kcal/mol), respectively, as compared with standard Celecoxib (-7.9 Kcal/mol) and the nonselective COX inhibitor Indomethacin (-6.4 Kcal/mol). Among the tested compounds, 9u has shown the highest activity with 65.6 % reduction in edema (69.8% for Celecoxib). Immunoassay results showed a significant drop in serum TNF-α and an elevation in serum IL-10. Conclusion: The findings highlight that some of the synthesized xanthone derivatives displayed marked anti-inflammatory activity, which can be further investigated to render efficient and novel non-ulcerogenic anti-inflammatory agents.

Loading

Article metrics loading...

/content/journals/lddd/10.2174/1570180818666210427093459
2021-09-01
2025-07-09
Loading full text...

Full text loading...

/content/journals/lddd/10.2174/1570180818666210427093459
Loading
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test