Title:Design, Synthesis, Computational and Biological Evaluation of Two New Series of 1, 3- and 1,6-dihydroxy Xanthone Derivatives as Selective COX-2 Inhibitors
Volume: 18
Issue: 9
Author(s): Urvashee Gogoi*, Aparoop Das, Manash Pratim Pathak, Pronobesh Chattopadhyay and Surabhi Johari
Affiliation:
- Department of Pharmaceutical Sciences, Dibrugarh University, Dibrugarh, Assam,India
Keywords:
Xanthone derivatives, computational chemistry, enzymes, anti-inflammatory, prostaglandins, ELISA.
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.
