Synthesis, characterization and urease inhibition studies of transition metal complexes of thioureas bearing ibuprofen moiety

Starting from ibuprofen, a non-steroidal anti-inflammatory drug, N,N'-disubstituted thiourea derivatives were synthesized by refluxing the acid chloride of ibuprofen with potassium thiocyanate followed by substituted anilines to get N-2-(4-(2-methylpropyl)phenyl)propionoyl-N´-(2´-bromophenyl) thiourea (1), N-2-(4-(2-methylpropyl)phenyl)propionoyl-N´-(2´-chlorophenyl) thiourea (2) and N-2-(4-(2-methylpropyl)phenyl)propionoyl-N´-(3´,4´-dichlorophenyl) thiourea (3). Metal complexes (4-15) of (1-3) were synthesized by refluxing it with one equivalence salts of Co (ΙΙ), Ni(ΙΙ), Pb(ΙΙ) and Cu(Ι). Structures of all the synthesized thiourea ligands and their metal complexes were determined by FTIR and ¹HNMR spectroscopy. Shift in stretching frequency in FTIR and resonance frequency in ¹HNMR spectroscopic data suggested that the ligands and metal are coordinated to afford respective metal complexes M[L]_n. The synthesized compounds were tested against urease enzyme and the results were compared with standard thiourea, as positive control. Most of the investigated compounds showed potential inhibitory activity against Jack bean urease. Compound 5 was found to be the most potent urease inhibitor with IC₅₀ of 14.6 µM, whereas compounds 8, 11 and 12 possessed potent urease inhibition. The tested compounds can be taken as lead molecules for gastrointestinal ulcer therapy.