Biology-oriented drug synthesis (BIODS), in vitro urease inhibitory activity, and in silico studies on ibuprofen derivatives

Abstract: Novel ibuprofen derivatives 1–19 including ibuprofen hydrazide 1, and substituted thiourea derivatives 2–19 were synthesized and characterized by EI-MS, FAB-MS, HREI-MS, HRFAB-MS, ¹H-, and ¹³C-NMR spectroscopic techniques. The synthetic molecules 1–19 were examined for their in vitro urease inhibition and were found to display a diversified degree of inhibitory potential in the range of IC₅₀ = 2.96–178 μM as compared to the standard thiourea (IC₅₀ = 21.32 ± 0.22 μM). Out of nineteen, thirteen derivatives 2–4, 6, 7, 9, 11–15, 17, and 18 demonstrated remarkable inhibitory activity with IC₅₀ values of 2.96 ± 1.11 to 16.1 ± 1.07 μM, compound 5 exhibited moderate inhibition with IC₅₀ value of 37.3 ± 0.41 μM, whereas, compounds 1, 8, and 10 demonstrated weak inhibition against urease enzyme. Almost all structural features are participating in the activity; however, limited structure–activity relationship was discussed on the basis of different structural features, i.e., different functional groups and their positions at aryl part. In addition, molecular docking study was performed in order to understand the ligands binding interactions with the active site of urease enzyme. Graphic abstract: [Figure not available: see fulltext.]