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

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, H-1-, and C-13-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 mu M as compared to the standard thiourea (IC50 = 21.32 +/- 0.22 mu M). 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 mu M, compound 5 exhibited moderate inhibition with IC50 value of 37.3 +/- 0.41 mu M, 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

Automated summary

Novel ibuprofen derivatives and substituted thiourea derivatives were synthesized and characterized, showing diverse inhibitory potential against urease enzyme. Thirteen derivatives displayed remarkable inhibitory activity, with limited structure-activity relationship discussions based on different structural features. Molecular docking study was conducted to investigate ligands binding interactions with the active site of urease enzyme.