Ruthenium(II) p-cymene complexes bearing amine-functionalized N-heterocyclic carbenes: Synthesis, characterization, in silico and enzyme inhibition studies

Although the ruthenium N-heterocyclic carbene (NHC) complexes have been widely used in catalysis, they have only recently been evaluated for medicinal applications. Herein, a series of new ruthenium(II) p-cymene complexes with benzimidazole-based NHC ligands were synthesized by the transmetalation reaction from silver(I)–NHC complexes. These complexes were characterized by FT-IR, 1H NMR and 13C NMR spectroscopy, elemental analysis, and mass spectrometry. Also, the molecular and crystal structures of 3f has been determined by the single-crystal X-ray diffraction method. Acetylcholinesterase (AChE) plays an important role in neurotransmission by hydrolyzing the neurotransmitter acetylcholine. On the other hand, carbonic anhydrase (CA) has a crucial role in living organisms for the maintenance of some obligatory metabolic functions. All the ruthenium(II) complexes were tested against the enzymes including AChE, hCAs I and II, which associated with epilepsy, glaucoma, and Alzheimer's disease (AD), respectively. These complexes 3a-f were recognized as highly potent inhibition effects towards hCA I isoenzyme (Kis: 2.80 ± 0.05–35.46 ± 9.07 μM) and hCA II isoenzyme (Kis: 4.52 ± 0.24–20.20 ± 2.28 μM) and AChE enzyme (Kis: 0.39 ± 0.21–1.31 ± 0.03 μM). Besides these, molecular docking simulations and the ADMET process, which are computational methods, were used to elucidate and verify the results obtained from the above-mentioned studies at the molecular level.