Selenourea and thiourea derivatives of chiral and achiral enetetramines: Synthesis, characterization and enzyme inhibitory properties.

A series of chiral and achiral cyclic seleno- and thiourea compounds bearing benzyl groups on N-atoms were prepared from enetetramines and appropriate Group VI elements in good yields. All the synthesized compounds were characterized by elemental analysis, FT-IR, 1H NMR and 13C NMR spectroscopy, and the molecular and crystal structures of (R,R)-4b and (R,R)-5b were confirmed by the single-crystal X-ray diffraction method. These assayed for their activities against metabolic enzymes acetylcholinesterase, butyrylcholinesterase, and α-glycosidase. These selenourea and thiourea derivatives of chiral and achiral enetetramines effectively inhibit AChE and BChE with IC50 values in the range of 3.32-11.36 and 1.47-9.73 µM, respectively. Also, these compounds inhibited α-glycosidase enzyme with IC50 values varying between 1.37 and 8.53 µM. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against α-glycosidase enzyme, (S,S)-5b, was 12-times more potent than standard inhibitor acarbose; 7b and 8a as most potent compounds against cholinesterase enzymes, were around 5 and 13-times more potent than standard inhibitor tacrine against achethylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively.

Phthalimide-tethered imidazolium salts: Synthesis, characterization, enzyme inhibitory properties, and in silico studies.

A series of new imidazolium salts were prepared in good yield by the reaction between 1-alkylimidazole and a variety of alkyl halides. The structures of the compounds were identified by FT-IR, 1 H NMR, and 13 C NMR spectroscopy, elemental analysis, and mass spectrometry. The crystal structure of 1b was determined by the single-crystal X-ray diffraction method. The phthalimide-tethered imidazolium salts exhibited inhibition abilities toward acetylcholinesterase (AChE) and human carbonic anhydrases (hCAs) I and II, with Ki values in the range of 24.63 ± 3.45 to 305.51 ± 35.98 nM for AChE, 33.56 ± 3.71 to 218.01 ± 25.21 nM for hCA I and 17.75 ± 0.96 to 308.67 ± 13.73 nM for hCA II. The results showed that the new imidazolium salts can play a key role in the treatment of Alzheimer's disease, epilepsy, glaucoma, and leukemia, which is related to their inhibition abilities of hCA I, hCA II, and AChE. Molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity studies were used to look into how the imidazolium salts interacted with the specific protein targets. To better visualize and understand the binding positions and the influence of the imidazolium salts on hCA I, hCA II, and AChE conformations, each one was subjected to molecular docking simulations.

Schiff bases and their amines: Synthesis and discovery of carbonic anhydrase and acetylcholinesterase enzymes inhibitors.

Three series of symmetrical Schiff bases were synthesized from 1,2-diaminoethane, 1,3-diaminopropane and 1,4-diaminobutane and substituted benzaldehydes, and reduced by sodium borohydride to the corresponding benzylic diamines 4-6. All of the compounds obtained were characterized using elemental analysis, FT-IR, 1 H NMR, and 13 C NMR spectroscopy. The enzyme inhibitory properties of these compounds were tested and the influence of the alkane chain length and the substituents on the phenyl group on the enzyme inhibition activity were examined. The novel Schiff bases and their amine derivatives (1a-d, 2a-d, 3b-d, 4a-c, 5a-c, 6a, 6c, 6d) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) with Ki values in the range of 159.43 ± 30.03 to 563.73 ± 115.30 nM for hCA I, 104.88 ± 18.44 to 524.32 ± 95.03 nM for hCA II, and 3.95 ± 0.74 to 30.83 ± 6.81 nM for AChE.

Enhanced π-back-donation resulting in the trans labilization of a pyridine ligand in an N-heterocyclic carbene (NHC) PdII precatalyst: a case study.

The molecular structure of the benzimidazol-2-ylidene-PdCl2-pyridine-type PEPPSI (pyridine-enhanced precatalyst, preparation, stabilization and initiation) complex {1,3-bis[2-(diisopropylamino)ethyl]benzimidazol-2-ylidene-κC2}dichlorido(pyridine-κN)palladium(II), [PdCl2(C5H5N)(C23H40N4)], has been characterized by elemental analysis, IR and NMR spectroscopy, and natural bond orbital (NBO) and charge decomposition analysis (CDA). Cambridge Structural Database (CSD) searches were used to understand the structural characteristics of the PEPPSI complexes in comparison with the usual N-heterocyclic carbene (NHC) complexes. The presence of weak C-H...Cl-type hydrogen-bond and π-π stacking interactions between benzene rings were verified using NCI plots and Hirshfeld surface analysis. The preferred method in the CDA of PEPPSI complexes is to separate their geometries into only two fragments, i.e. the bulky NHC ligand and the remaining fragment. In this study, the geometry of the PEPPSI complex is separated into five fragments, namely benzimidazol-2-ylidene (Bimy), two chlorides, pyridine (Py) and the PdII ion. Thus, the individual roles of the Pd atom and the Py ligand in the donation and back-donation mechanisms have been clearly revealed. The NHC ligand in the PEPPSI complex in this study acts as a strong σ-donor with a considerable amount of π-back-donation from Pd to Ccarbene. The electron-poor character of PdII is supported by π-back-donation from the Pd centre and the weakness of the Pd-N(Py) bond. According to CSD searches, Bimy ligands in PEPPSI complexes have a stronger σ-donating ability than imidazol-2-ylidene ligands in PEPPSI complexes.

The effect of prilocaine and prilocaine plus meperidine infiltration on the pain during nasal packing removal.

OBJECTIVE: Removing the nasal packing after nasal surgery is an uncomfortable and painful procedure. Since there is no controlled trial described in the literature about the local use of meperidine during packing removal, we aimed to compare the analgesic and sedative effects of the meperidine-prilocaine combination, injected into the packing 15 minutes before the procedure, with that of prilocaine during packing removal. METHODS: Fifty adult patients, for whom nasal packing removal after nasal septoplasty was scheduled, were randomly allocated into one of two groups. In the prilocaine group (Group P, n = 25), 5 ml of 1% prilocaine in saline was injected into the pack 15 minutes before removal. In the prilocaine-meperidine group (Group MP, n = 25), 5 ml fluid combination containing prilocaine (10 mg/ml) and meperidine (1 mg/kg) was injected in nasal packs. Five ml saline was injected into the package in the contra-lateral nostril in both groups as control. Visual analogue scale (VAS) score was recorded during injections (t) and packing removal (t), and the Ramsay sedation score was evaluated. RESULTS: VAS score was not different from the control nostril in Group P (p > 0.05), where as it was significantly lower than the control nostril in Group MP (p < 0.05). Ramsay sedation scores were significantly higher in Group MP compared to the control nostril and actively treated nostril of Group P (p < 0.05). CONCLUSION: The injection of prilocaine plus meperidine into the nasal pack 15 minutes before nasal packing removal provides effective analgesia and mild sedation during the procedure.

Acquired toxoplasmosis of the buccal area with extranodular involvement: report of an unusual case.

Acquired toxoplasmosis is a common parasitic infection in humans. It can be caused by ingestion of infected meat or other food that has been contaminated by the feces of infected cats. Approximately 90% of immunocompetent patients with acquired toxoplasmosis are asymptomatic and undiagnosed; in the other 10%, toxoplasmosis manifests as a nonspecific, self-limited illness that usually does not require treatment. In symptomatic cases, cervical lymphadenopathy is one of the most common clinical findings. We report the case of a 33-year-old woman who experienced unilateral facial swelling secondary to toxoplasmosis. In addition to the atypical location of her disease (i.e., the buccal area), the atypical histopathologic findings in this case (e.g., extranodular involvement) constituted a very unusual presentation of toxoplasmosis.