Synthesis, characterization, biological evolution and docking study of Resorcin[4]arene hybrid thymine acetic acid derivatives

Resorcin[4]arenes are an important class of supramolecular macrocycles possessing remarkable host-guest recognition properties and broad pharmacological potential. In the present study, a novel series of resorcin[4]arene-thymine acetic acid hybrid derivatives (6a–k) was synthesized through an efficient coupling strategy employing microwave-assisted synthesis and DCC/DMAP-mediated esterification. All synthesized compounds were purified by column chromatography and comprehensively characterized using FT-IR, 1H-NMR, 13C-NMR, mass spectrometry, and elemental analysis. The synthesized derivatives were evaluated for their antibacterial, antifungal, antimalarial, antitubercular, and antioxidant activities. Several compounds exhibited promising biological profiles, particularly compounds 6b, 6f, and 6j, which demonstrated significant antimicrobial and antioxidant activities. Molecular docking studies against PDB targets 4N0K and 2H6S revealed favourable binding interactions and strong binding affinities, especially for compound 6b. The results indicate that these resorcin[4]arene-thymine hybrids may serve as promising lead molecules for the development of novel supramolecular therapeutic agents.