Himanshu Sharma, Viney Lather*, Ajmer Singh Grewal and Deepti Pandita Pages 225 - 234 ( 10 )
Background: Phosphodiesterase 4 (PDE4) and phosphodiesterase 7 (PDE7), PDE superfamily members, increase inflammatory processes in immunomodulatory as well as pro-inflammatory cells via breakdown of cyclic adenosine monophosphate. Dual inhibitors of PDE4 and PDE7 are a novel class of drug candidates which can regulate pro-inflammatory as well as T-cell function and can be particularly advantageous in the treatment of a wide-ranging disorders associated with the immune system as well as inflammatory diseases with fewer unwanted adverse effects.
Objective: The current research work was planned to design and synthesize some newer substituted 1,3- thiazolidine-2,4-dione derivatives as dual inhibitors of PDE4 and PDE7 followed by evaluation of their anti-inflammatory activity and in silico docking studies.
Methods: A new series of substituted 1,3-thiazolidine-2,4-dione derivatives was synthesized followed by evaluation of their anti-inflammatory activity in animal models. In silico docking studies were performed for the evaluation of the binding pattern of synthesized derivatives in the binding site of both PDE4 and PDE7 proteins.
Results: Amongst the newly synthesized derivatives, compounds 5 and 12 showed higher antiinflammatory activity in the animal model. The results of in vivo animal studies were found to be in concordance with the results of molecular docking studies.
Conclusion: These newly synthesized derivatives can act as the lead molecules for the design of safe and therapeutically effective agents for various inflammatory diseases acting via inhibition of both PDE4 and PDE7.
Anti-inflammatory activity, cAMP, dual PDE4 and PDE7 inhibitors, inflammation, thiazolidinedione derivatives, docking studies.
Jan Nayak Ch. Devi Lal Memorial College of Pharmacy, Sirsa 125055, Haryana, Jan Nayak Ch. Devi Lal Memorial College of Pharmacy, Sirsa 125055, Haryana, Chitkara College of Pharmacy, Chitkara University, Rajpura, Patiala 140401, Punjab, Jan Nayak Ch. Devi Lal Memorial College of Pharmacy, Sirsa 125055, Haryana