Design, synthesis, biological assessment, and molecular docking of pyrrole-derived Bis-Schiff bases as potential urease inhibitors

A series of fifteen N-substituted pyrrole-based bis-Schiff bases (1–15) were synthesized and structurally confirmed using techniques such as ¹H NMR, ¹³C NMR, and HREI-MS. These compounds were assessed for urease inhibition activity. Except for analogues 1 and 6, all analogues showed inhibitory potential with IC₅₀ values ranging from 4.11 ± 0.10 to 28.22 ± 0.30 µM, compared to the standard drug thiourea (IC₅₀ = 21.86 ± 0.40 µM). Compounds 5, 9, 11, and 12 exhibited notably higher activity, with IC₅₀ values of 9.21 ± 0.10, 7.65 ± 0.11, 4.11 ± 0.10, and 5.36 ± 0.10 µM, respectively. Structure–activity relationship analysis indicated that the nature, number, and position of substituents on the phenyl ring significantly affected activity. Molecular docking studies further supported the observed biological results by revealing strong interactions of the most active compounds within the urease active site.