Synthesis of novel 3-bromosulfanilamide acyl thiourea derivatives: a study on urease inhibition and their molecular docking

In this work, it is designed and synthesized therapeutically active anti-urease agents based on 3-bromosulfanilamide-based acyl thioureas (4a-j) through reaction of brominated sulfanilamide with aromatic acids via isothiocyanate formation and characterized by using FT-IR, 1HNMR, ¹³C NMR and MS analysis. The freshly prepared compounds were screened for in vitro urease inhibition assay. The derivative 4a with an un-substituted phenyl group showed IC₅₀ value of 17.02 ± 0.011 against urease as compared to the standard thiourea (IC₅₀ = 21 ± 0.12 µM). Structure activity relationship (SAR) revealed that the electronic and positional effects of substituents on phenyl ring play important role for the inhibition of clinically important enzymes. Additionally, in silico investigation was carried out which demonstrated that the compounds have exhibited polar and nonpolar interaction with the crucial residues in the binding site of urease. The in vitro and in silico studies are in agreement as per kinetics and docking results indicating that the synthesized 3-bromosulfanilamide-based acyl thiourea derivatives may serve as potential hits for the discovery of new urease inhibitors.