Synthesis and Biological Evaluation of Schiff Base Derivatives Exhibiting Antimicrobial, Antifungal, and Antibiofilm Activities Supported by Molecular Docking

ABSTRACT In this study, fourteen Schiff base derivatives ( 3a‐g and 5a‐g ) were synthesized following the reactions of substituted benzaldehydes with furfurylamine or 2‐thiophenamine. The structures of the synthesized compounds were elucidated using NMR, FTIR, GC‐MS, and elemental analysis techniques, and the products were purified by crystallization. Following the syntheses, the antimicrobial, antifungal, and antibiofilm activities of all molecules were examined, and the MIC 99 values of the active molecules were calculated. When the biological activity results were examined, it was determined that the furfurylamine derivatives showed moderate activity and that compound 3b was the most active. In contrast to the furfurylamine derivatives, the 2‐thiophenamine derivatives showed higher biological activity, with compounds 5f and 5 g demonstrating particularly high efficacy against all tested strains. A structure‐activity relationship determined based on the biological activity results of molecules with the same skeleton structure but different side groups has revealed that biological activity is significantly dependent on side groups. It has been found that electron‐donating groups (OH and OMe) and halogens (Br and Cl) attached to the thiophene skeleton significantly increase activity. The fact that the 5c molecule, which contains no side groups, has no biological activity supports these findings. Molecular docking studies conducted for the most active molecules have supported the experimental results obtained. In general, this study clearly demonstrates the interaction between substituted groups and heteroaromatic structures in determining antimicrobial activity.