Facile Synthesis, Characterization and in Silico Docking Studies of Novel Thiazolidine-2,4-Dione-Based Mannich Base Bearing Furan/Thiophene Moiety as Promising Anti-Inflammatory Agents

Abstract

Mannich bases are compounds bearing a β-amino carbonyl moiety. They are formed in the Mannich reaction that consists of an amino alkylation of an acidic proton placed next to a carbonyl functional group by formaldehyde and a primary or secondary amine. Mannich base products are known for their curative properties such as anti-inflammatory, antibacterial, anticancer, antifungal, anthelmintic, anticonvulsant, analgesic, anti-HIV, antipsychotic, antiviral, and antimalarial activities. Further, thiazolidinedione derivatives have shown to be efficacious in inflammatory diseases as wide-ranging as psoriasis, ulcerative colitis and non-alcoholic steatohepatitis. In light of the above observations, new series of thiazolidine-2,4-dione based Mannich base derivatives were synthesized via a simple and catalyst-free procedure involving the condensation of thiazolidine-2,4-dione, formaldehyde and secondary amines in DMF solvent. The structures of the newly synthesized compounds were confirmed by their IR, 1H-NMR, and Mass spectra. The synthesized compounds were tested for their in silico anti-inflammatory activity by Docking studies against COX-2 enzyme (PDB: 1CX2). Compounds 4a and 4b showed good in silico anti-inflammatory properties comparable to that of standard drug Diclofenac and may be considered as promising candidates for the development of new anti-inflammatory agents.