Synthesis, Anti-inflammatory Activity and Docking Studies of Some Newer 1,3-Thiazolidine-2,4-dione Derivatives as Dual Inhibitors of PDE4 and PDE7.

BACKGROUND: Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), members of PDE superfamily, catalyse hydrolysis of cyclic adenosine monophosphate in pro-inflammatory and immunomodulatory cells leading to increased inflammatory processes. Dual inhibitors of PDE4 and PDE7 are a novel class of drug candidates which can regulate pro-inflammatory as well as immune T-cell function and can be particularly useful in the treatment of a wide variety of immune and inflammatory disorders with less undesirable adverse effects.

OBJECTIVE: The present research work was designed to synthesize and evaluate the anti-inflammatory activity as well as in silico docking studies of some newer substituted 1,3-thiazolidine-2,4-dione derivatives as dual inhibitors of PDE4-PDE7.

METHOD: A new series of substituted 1,3-thiazolidine-2,4-dione derivatives was synthesized and evaluated for anti-inflammatory activity in animal models followed by docking studies to determine the binding interactions for the best fit conformations in the binding site of PDE4 and PDE7 proteins.

RESULTS: Amongst the synthesized molecules, compounds 5 and 12 showed higher anti-inflammatory activity in the carrageenan induced rat paw oedema method. The in vivo experimental results were found to be in concordance with that of the in silico results.

CONCLUSION: These molecules can act as the starting hits for the design of safe and effective dual inhibitors of PDE4 and PDE7 for the potential treatment of various inflammatory disorders.