Imidazole Moiety Research Articles

Assembly of isoxazol-5-one with 2-unsubstituted imidazole N-oxides and aldehydes.

A new synthetic protocol has been developed to construct polyfunctional isoxazol-5-one derivatives with imidazole moiety. It is based on the Knoevenagel condensation of isoxazol-5-one with aldehydes and subsequent Michael addition of imidazole N-oxides as part of a tandem three-component process. This reaction proceeds smoothly in moderate-to-good yield under catalyst-free conditions.

Hyaluronidase-trigger nanocarriers for targeted delivery of anti-liver cancer compound.

Chemotherapy is recognized as one of the significant treatment methods for liver cancer. The compound celastrol (CSL) could effectively inhibit the proliferation, migration, and invasion of liver cancer cells, which is regarded as a promising candidate to become a mainstream anti-liver cancer drug. However, the application of CSL in liver cancer chemotherapy is limited due to its systemic toxicity, poor water solubility, multidrug resistance, premature degradation, and lack of tumor targeting. Meanwhile, in order to comply with the current concept of precision medicine, precisely targeted delivery of the anti-liver compound CSL was desired. This paper takes into account that liver cancer cells were equipped with hyaluronic acid (HA) receptors (CD44) on their surface and overexpressed. Hyaluronidase (HAase) capable of degrading HA, HAase-responsive nanocarriers (NCs), named HA/(MI)7-β-CD NCs, were prepared based on the electrostatic interaction between HA and imidazole moieties modified β-cyclodextrin (MI)7-β-CD. HA/(MI)7-β-CD NCs showed disassembly properties under HAase stimuli, which was utilized to trap, deliver, and the controllable release of the anti-liver cancer compound CSL. Furthermore, cytotoxicity assay experiments revealed that CSL-trapped HA/(MI)7-β-CD NCs not only reduced cytotoxicity for normal cells but also effectively inhibited the survival for five tumor cells, and even the apoptotic effect of CSL-trapped NCs with a concentration of 5 μg mL-1 on tumor cells (SMMC-7721) was consistent with free CSL. Cell uptake experiments demonstrated HA/(MI)7-β-CD NCs possessed the capability of targeted drug delivery to cancerous cells. HA/(MI)7-β-CD NCs exhibited site-specific and controllable release performance, which is anticipated to proceed further in precision-targeted drug delivery systems.

Synthesis and immunopharmacological evaluation of novel TLR7 agonistic triazole tethered imidazoquinolines.

Toll-like receptors-7 and -8 are expressed abundantly on antigen-presenting cells, and their agonists make potential adjuvant candidates for the development of new efficacious vaccines. In view of the importance of new efficacious imidazoquinoline based adjuvants, herein we have synthesized a focused library of a new class of imidazoquinolines retaining the N-isobutyl substitution of an imidazole moiety as in imiquimod and introduced a 1,2,3-triazolyl moiety upon alkyl substitution at the imidazolemethyne carbon employing triazolyl click chemistry. All the novel analogues were characterized using various spectroscopic techniques and the target specificity of these molecules was determined using HEK TLR7/8 transfected cell lines. TLR7/8 activity and also the molecular docking results correlated primarily to the position of the substituent for aromatic groups and also to the chain length in alkyl substitutions. The immunomodulatory properties of these analogues were evaluated using murine DC activation and also with hPBMC activation markers, cytokines which revealed that these analogues after modification were able to target the TLR7 receptors and also had a pro-inflammatory immune response.

A Simple Substitution on Thyroid Hormones Remarkably Alters the Regioselectivity of Deiodination by a Deiodinase Mimic.

The regioselective deiodinations of L-thyroxine (T4) play key roles in the thyroid hormone homeostasis. These reactions are catalyzed by three isoforms of the selenoenzymes, iodothyronine deiodinases (Dio1, Dio2 and Dio3), which are highly homologous in nature. Dio1 mediates 5'- or 5-deiodinations of T4 to produce T3 and rT3, respectively. In contrast, Dio2 and Dio3 are selective to 5'- or 5-deiodination to produce T3 and rT3, respectively. Understanding of the regioselectivity of deiodination at the molecular level is important as abnormal levels of thyroid hormone have been implicated in various clinical conditions, such as hypoxia, myocardial infarction, neuronal ischemia and cancer. In this paper, we report that the electronic properties of the iodine atoms in thyroxine (T4) can be modulated through a simple substitution in the 4'-phenolic moiety. This leads to the change in the regioselectivity of deiodination by different small molecule mimics of Dio enzymes. By using this chemical approach, we also show that the substitution of a strong electron withdrawing group facilitates the removal of all four iodine atoms in the T4 derivative. Theoretical investigations on the hydrogen bonded adducts of T4 with imidazole indicate that the charge on the iodine atoms depend on the nature of hydrogen bond between the -OH group of T4 and the imidazole moiety. While the imidazole can act as either hydrogen bond acceptor (HBA) or hydrogen bond donor (HBD), the protonated imidazole acts exclusively as HBD in T4-imidazole complex. These studies support the earlier observations that the histidine residue at the active sites of the deiodinases play an important role not only in the substrate binding, but also in altering the regioselectivity of the deiodination reactions.

A Facile Synthesis of Thiazole Derivatives bearing Imidazole Moiety, Schiff Bases and their O-Glucosides

A unique approach for the synthesis of new thiazole O-glycosides is presented in this work. 2-Amino-4-hydroxy-phenyl-1,3-thiazole-5-carboxaldehyde (3a) was reacted with phenyl glyoxal and benzil to form 4-(4-hydroxy-phenyl)-5-(4-phenyl-1H-imidazol-2-yl)-thiazol-2-amine (4a) and 4-(4-hydroxy-phenyl)-5-(4,5-diphenyl-1H-imidazol-2-yl)-thiazol-2-amine (4b), respectively. A series of substituted Schiff bases of 4a and 4b were synthesized reacting with various aryl aldehyde to form 2-(imino substituted benzal)-4-(4-hydroxy-phenyl)-5-(4-phenyl-1H-imidazol-2-yl)-thiazoles (5a-e) and 2-(imino substituted benzal)-4-(4-hydroxy-phenyl)-5-(4,5-diphenyl-1H-imidazol-2-yl)-thiazoles (5f-j). Glucosylation of compounds (5a-j) have been done by using acetobromoglucose as glucosyl donor to afford 2-(imino substituted benzal)-4-(2,3,4,6-tetra-O-acetyl-p-O-β-D-glucosidoxyphenyl)-5-(4-phenyl- 1H-imidazol-2-yl)-thiazoles (6a-e) and 2-(imino substituted benzal)-4-(2,3,4,6-tetra-O-acetyl-p-O-β- D-glucosidoxyphenyl)-5-(4,5-diphenyl-1H-imidazol-2-yl)-thiazoles (6f-j) further on deacetylation to produce 2-(imino substituted benzal)-4-(p-O-β-D-glucosidoxyphenyl)-5-(4-phenyl-1H-imidazol-2-yl)- thiazoles and 2-(imino substituted benzal)-4-(p-O-β-D-glucosidoxyphenyl)-5-(4,5-diphenyl-1Himidazole- 2-yl)-thiazoles (7f-j). The synthesized compounds were characterized by elemental analyses, FTIR, 1H & 13C NMR and electron mass spectra (EI-MS) techniques and then screened for their in vitro antimicrobial activity.

Atomically precise binding conformations of adenine and its variants on gold using single molecule conductance signatures.

We demonstrate single molecule conductance as a sensitive and atomically precise probe of binding configurations of adenine and its biologically relevant variants on gold. By combining experimental measurements and density functional theory (DFT) calculations of single molecule-metal junction structures in aqueous conditions, we determine for the first time that robust binding of adenine occurs in neutral or basic pH when the molecule is deprotonated at the imidazole moiety. The molecule binds through the donation of the electron lone pairs from the imidazole nitrogen atoms, N7 and N9, to the gold electrodes. In addition, the pyrimidine ring nitrogen, N3, can bind concurrently and strengthen the overall metal-molecule interaction. The amine does not participate in binding to gold in contrast to most other amine-terminated molecular wires due to the planar geometry of the nucleobase. DFT calculations reveal the importance of interface charge transfer in stabilizing the experimentally observed binding configurations. We demonstrate that biologically relevant variants of adenine, 6-methyladenine and 2'-deoxyadenosine, have distinct conductance signatures. These results lay the foundation for biosensing on gold using single molecule conductance readout.

Syntheses, crystal structure, luminescent behaviors and Hirshfeld surface of salts with imidazole and benzimidazole-yl scaffolds

To explore the new photoluminescent materials, two new salts with imidazole and benzimidazole moieties, namely, [HIBI]+Z− (Z= MBS– (1) and BS– (2) [IBI = 2-((1H-imidazol-1-yl)methyl)-1H-benzimidazole, MBS = p-methyl phenyl sulfonic acid, BS= benzene-sulfonic acid], were obtained through reacting IBI and phenyl sulfonic acids by slow evaporation method, respectively. Compounds 1 and 2 have been characterized by single-crystal X-ray diffraction, IR, powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). In both compounds, a set of hydrogen bonds (C/N–H⋯O) can be evidently observed, through which a three-dimensional framework will be fabricated. The luminescent spectra show that the emission maximal peaks in compounds 1 and 2 can be observed to be 460 and 477 nm, respectively. By comparison with the free IBI, the emission maxima of compounds 1 and 2 are obviously red-shifted about 151 and 168 nm, respectively. The Hirshfield surface analysis further confirms that the C∙∙∙C close contacts can account for the photoluminescent spectra.

Derivatives of Imidazole and Carbazole as Bifunctional Materials for Organic Light-Emitting Diodes.

New derivatives of carbazole and diphenyl imidazole for potential multiple applications were synthesized and investigated. Their properties were studied by thermal, optical, photophysical, electrochemical, and photoelectrical measurements. The compounds exhibited relatively narrow blue light-emission bands, which is favorable for deep-blue electroluminescent devices. The synthesized derivatives of imidazole and carbazole were tested as fluorescent emitters for OLEDs. The device showed deep-blue emissions with CIE color coordinates of (0.16, 0.08) and maximum quantum efficiency of 1.1%. The compounds demonstrated high triplet energy values above 3.0 eV and hole drift mobility exceeding 10-4 cm2/V·s at high electric fields. One of the compounds having two diphenyl imidazole moieties and tert-butyl-substituted carbazolyl groups showed bipolar charge transport with electron drift mobility reaching 10-4 cm2/V·s at electric field of 8 × 105 V/cm. The synthesized compounds were investigated as hosts for green, red and sky-blue phosphorescent OLEDs. The green-, red- and sky-blue-emitting devices demonstrated maximum quantum efficiencies of 8.3%, 6.4% and 7.6%, respectively.

2,5-Disubstituted furan derivatives containing imidazole, triazole or tetrazole moiety as potent α-glucosidase inhibitors

α-Glucosidase inhibitors (AGIs) are oral antidiabetic drugs, preferably used in treating type 2 diabetes mellitus, that delay the absorption of carbohydrates from the gastrointestinal system. In this work, 2,5-disubstituted furan derivatives containing imidazole, triazole or tetrazole moiety (III-01 ∼ III-45) were synthesized and characterized by elemental analysis, HRMS, 1H NMR, 13C NMR and single crystal X-ray. Their inhibitory activity against α-glucosidase was screened. The most promising inhibitors were compound III-11 (IC50 = 6.0 ± 1.1 μM), III-16 (IC50 = 2.2 ± 0.2 μM) and III-39 (IC50 = 4.6 ± 1.9 μM), respectively. Kinetic study revealed that compounds III-11 and III-39 were uncompetitive inhibitors against α-glucosidase. Meanwhile, III-16 (Ki = 5.1 ± 0.7 μM) was a competitive inhibitor. Furthermore, molecular docking studies indicated that the existence of the azole group played a critically important role in hydrogen bond interaction with α-glucosidase. Significantly, in vivo toxicity towards HEK293 cells, RAW264.7 cells and HepG2 cells suggested that compounds III-11 and III-39 possessed non-toxicity, that could be considered as potential candidates for further development of novel antidiabetic drugs.

Nanoporous Alumina Support Covered by Imidazole Moiety-Based Ionic Liquids: Optical Characterization and Application.

This work analyzes chemical surface and optical characteristics of a commercial nanoporous alumina structure (NPAS) as a result of surface coverage by different imidazolium-based ionic liquids (1-butyl-3-metylimidazolium hexafluorophosphate, 3-methyl-1-octylimidazolium hexafluorophosphate, or 1-ethyl-3-methylimidazolium tetrafluoroborate). Optical characteristics of the IL/NPAS samples were determined by photoluminescence (at different excitation wavelengths (from 300 nm to 400 nm), ellipsometry spectroscopy, and light transmittance/reflectance measurements for a range of wavelengths that provide information on modifications related to both visible and near-infrared regions. Chemical surface characterization of the three IL/NPAS samples was performed by X-ray photoelectron spectroscopy (XPS), which indicates almost total support coverage by the ILs. The IL/NPAS analyzed samples exhibit different photoluminescence behavior, high transparency (<85%), and a reflection maximum at wavelength ~380 nm, with slight differences depending on the IL, while the refractive index values are rather similar to those shown by the ILs. Moreover, the illuminated I−V curves (under standard conditions) of the IL/NPAS samples were also measured for determining the efficiency energy conversion to estimate their possible application as solar cells. On the other hand, a computational quantum mechanical modeling method (DFT) was used to establish the most stable bond between the ILs and the NPAS support.

Functionalization of imidazole N-oxide: a recent discovery in organic transformations.

Nowadays heterocyclic compounds are widely used in medicinal chemistry and industry to develop life-saving drugs and medicines. Imidazole is one of the pharmacologically important heterocyclic motifs found in widely used and well-known medicines and bioactive molecules. The applications of imidazole derivatives displaying various biological activities, motivated researchers for the development of more potent and significant drugs containing imidazole moieties. The formation of imidazole derivatives can be achieved using imidazole N-oxide as starting material. In this review, the scope of substrates and reaction mechanisms of various synthetic approaches using imidazole N-oxides as substrates are summarized so that the chemists, researchers, and pharmaceutical industries find its effectiveness in near future for the synthesis of potent, novel, and non-toxic drug molecules.

Synthetic Imidazopyridine-Based Derivatives as Potential Inhibitors against Multi-Drug Resistant Bacterial Infections: A Review.

Fused pyridines are reported to display various pharmacological activities, such as antipyretic, analgesic, antiprotozoal, antibacterial, antitumor, antifungal, anti-inflammatory, and antiapoptotic. They are widely used in the field of medicinal chemistry. Imidazopyridines (IZPs) are crucial classes of fused heterocycles that are expansively reported on in the literature. Evidence suggests that IZPs, as fused scaffolds, possess more diverse profiles than individual imidazole and pyridine moieties. Bacterial infections and antibacterial resistance are ever-growing risks in the 21st century. Only one IZP, i.e., rifaximin, is available on the market as an antibiotic. In this review, the authors highlight strategies for preparing other IZPs. A particular focus is on the antibacterial profile and structure-activity relationship (SAR) of various synthesized IZP derivatives. This research provides a foundation for the tuning of available compounds to create novel, potent antibacterial agents with fewer side effects.

Recent Advances in Ultrasound Assisted Synthesis of 2,4,5-Trisubstituted Imidazoles: A Comparative Study of Effective Catalytic Systems

The imidazole moiety finds itself in a host of compounds having profound biological and medicinal properties. This has led to the quest to develop a cost effective, and desirably greener synthetic route to access this azole. In this review, ultrasonic irradiation assisted syntheses of trisubstitued imidazole derivatives have been discussed which make use of different environment friendly and efficient catalytic systems. They have been found to give excellent yield of product having high purity and with a shorter reaction time and has proved to be a viable alternative to traditional methods.

STEM-19. LIVE DETECTION OF NEURAL STEM AND GLIOBLASTOMA CELLS BY A LUMINESCENT CONJUGATED OLIGOTHIOPHENE DERIVATIVE

Abstract Glioblastoma (GBM) is an aggressive nervous system tumor with a mean survival time of 12-14 months. Cells with neural stem cell-like properties can be derived from GBM tumors. These cells seem to escape conventional irradiation treatment, chemotherapy, and surgery, and may play a crucial role for relapse. It is therefore urgent to develop novel approaches for reliable detection of neural stem cell-like cells in GBM. Here we report a luminescent conjugated oligothiophene (LCO), named GlioStem (p-HTMI), for non-invasive and non-amplified real-time detection of live human patient-derived GBM cells and embryonic neural stem/progenitor cells (NSPCs). Within a maximum of 10 minutes after administration of the molecule in vitro, in the existing media, fluorescence emission was observed without any modulation of the cells or additional vehicle, resulting in efficient detection of cytoplasmic luminescent signal in NSPCs or GBM cells from rodents and humans, detectable at Alexa488/GFP wavelength. GlioStem is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. In vitro, GlioStem was shown to identify fetal cortical NSPCs from rat (FGF2-expanded), embryonic stem cell-derived NSPCs from mouse (FGF2/EGF-expanded), and FGF2-exposed C6 glioma cell cultures from rat, but not any other cell types investigated. Cell sorting experiments of patient-derived, FGF2/EGF-expanded GBM cells demonstrated that GlioStem in addition to NSPC-markers like Nestin and Sox2 labeled the same population (overlap &amp;gt; 90%) of cells as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO GlioStem is a versatile tool for immediate and selective detection of subpopulations of neural stem and glioma cells.

Bidentate and tridentate coordination modes of bis(3-methylindolyl)-2-(1-methylimidazolyl)methane in complexes of aluminum and gallium

Bis(3-methylindolyl)-2-(1-methylimidazolyl)methane (1) was synthesized by acid-catalyzed condensation of methyl-2-formylimidazole and two equivalents of 3-methylindole, followed by deprotonation of the imidazole moiety of the protonated compound, [(1-CH3C3H2N2H)HC(3-CH3C8H4NH)2][HSO4] ([1•H][HSO4 ]). Reactions of a trialkylaluminum or tri‑tert-butylgallium with 1 produced complexes (1-CH3C3H2N2)HC(3-CH3C8H4N)(3-CH3C8H4NH)MR2 (M = Al, R = Me (2a), Et (2b), iBu (2c), tBu (2d); M = Ga, R = tBu (3)) in which mono-deprotonated 1 adopts a bidentate coordination mode. Thermolysis of 2a-2d or 3 in refluxing toluene did not result in further alkane elimination. Deprotonation of 1 with two equivalents of nBuLi followed by reaction with an alkylaluminum dichloride yielded monomeric, tripodal complexes (1-CH3C3H2N)HC(3-CH3C8H4N)2MR (M = Al, R = Me (4a), Et (4b), iBu (4c), tBu (4d)) in which bis-deprotonated 1 adopts a tridentate coordination mode. Reaction of 1 with two equivalents of trimethylaluminum or triethylaluminum yields dialuminum complexes (1-CH3C3H2N)HC(3-CH3C8H4N)2Al2R4 (R = Me (5a), Et (5b). In addition to NMR (1H, 13C) spectroscopy, compounds 1, 2d, 3, and 4b were further characterized by X-ray crystallography as CH2Cl2 or toluene solvates.

Efficient and Stable Mesoporous CsSnI3 Perovskite Solar Cells via Imidazolium‐Based Ionic Liquid Additive

Inorganic tin halide perovskite compound with its eco‐friendly property has attracted tremendous attention of researchers in the field of lead‐free perovskite solar cells. However, the trap‐assisted nonradiative recombination caused by deep‐level defects originating from surface undercoordinated Sn2+ cations significantly deteriorates the CsSnI3 device's performance. Herein, adding low concentrations of an ionic liquid 1‐ethyl‐3‐methylimidazolium acetate (EMIMAc) shows promise in controlling deep‐level defects in CsSnI3 perovskites. Both experimental observation and theoretical simulation reveal that EMIMAc can have strong electrostatic attraction and coordination interaction with the surface undercoordinated Sn2+ through the lone electron pairs of carboxyl functional groups and the donated π electrons from electron‐rich imidazole moieties, leading to a reduced deep‐level defect density and a restrained nonradiative recombination. Consequently, the processed CsSnI3 perovskite solar cells based on a printable fluorine‐doped tin oxide/compact‐TiO2/mesoporous‐TiO2/Al2O3/NiO/carbon framework achieve a power conversion efficiency as high as 8.54%, which is the champion efficiency among all the reported CsSnI3 mesoporous perovskite solar cells up to now. In addition, the unencapsulated devices have shown an impressive long‐term stability with only ≈6% efficiency degradation after over 2000 h aging under nitrogen atmosphere.

SAR exploration of the non-imidazole histamine H3 receptor ligand ZEL-H16 reveals potent inverse agonism.

Histamine H3 receptor (H3 R) agonists without an imidazole moiety remain very scarce. Of these, ZEL-H16 (1) has been reported previously as a high-affinity non-imidazole H3 R (partial) agonist. Our structure-activity relationship analysis using derivatives of 1 identified both basic moieties as key interaction motifs and the distance of these from the central core as a determinant for H3 R affinity. However, in spite of the reported H3 R (partial) agonism, in our hands, 1 acts as an inverse agonist for Gαi signaling in a CRE-luciferase reporter gene assay and using an H3 R conformational sensor. Inverse agonism was also observed for all of the synthesized derivatives of 1. Docking studies and molecular dynamics simulations suggest ionic interactions/hydrogen bonds to H3 R residues D1143.32 and E2065.46 as essential interaction points.

Transition metal complexes of imidazole derived Schiff bases: Antioxidant/anti-inflammatory/antimicrobial/enzyme inhibition and cytotoxicity properties

A flexible class of Ni(II) and Zn(II) complexes were prepared with a novel Schiff base ligand containing imidazole moiety. The synthesized compounds were taken for structural characterizations such as elemental analysis, UV-Vis, FT-IR, 1H and 13C NMR, mass spectra, thermogravimetric investigation, magnetic susceptibility, and conductivity estimations. The coordination building of Ni(II) and Zn(II) complexes were found as octahedral and tetrahedral where Ni(II) and Zn(II) metal ions were composed by a nitrogen atom of the azomethine, imidazole ring, and oxygen atom of acetate derivative. All of the synthesized compounds were tried for their biochemical properties, including antioxidant, anti-inflammatory, antimicrobial activities, enzyme inhibition, and cytotoxicity. The antioxidant activity of designed compounds was screened by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) technique and all the Schiff base ligand and some of its Ni(II)/Zn(II) complexes showed close antioxidant activities against the standards (BHA, BHT, and ascorbic acid). Anti-inflammatory activity was estimated by the in-vitro human red blood cell (HRBC) membrane stabilization method, the Zn(II) complexes exhibited more activity for inflammation compared with Diclofenac, which is used as a standard drug. The in-vitro antimicrobial movement of synthesized compounds have been examined in microorganisms like Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Streptococcus mutans, Enterobacter cloacae, Aspergillus niger and Candida albicans by agar disk diffusion method. Nystatin and Ciprofloxacin were selected as reference drugs. Enzyme inhibitions of the Schiff bases and their metal complexes were investigated using α-amylase and the best inhibition value (Ki) was observed for the Ni(II)/Zn(II) complex of 4-[(5-methyl-3H-imidazole-4-ylmethylene)-amino]-2-nitro-phenol (MINPN/MINPZ) (0.022/0.020 mM) with Acarbose as standard compound. The cytotoxic behavior of synthesized compounds was evaluated against cancer cell lines: DLA cells (Trypan blue exclusion method) and HepG2 cells (MTT assay) and determined the cell viability of the respective human cell, H9c2 via MTT assay. Encouragingly, most of the compounds are generally non-toxic, to the human cells, H9c2.

Molecular insights into the binding of carnosine and anserine to human serum carnosinase 1 (CN1)

Carnosine (CAR) and anserine (ANS) are histidine-containing dipeptides that show the therapeutic properties and protective abilities against diabetes and cognitive deficit. Both dipeptides are rich in meat products and have been used as a supplement. However, in humans, both compounds have a short half-life due to the rapid degradation by dizinc carnosinase 1 (CN1) which is a hurdle for its therapeutic application. To date, a comparative study of carnosine- and anserine-CN1 complexes is limited. Thus, in this work, molecular dynamics (MD) simulations were performed to explore the binding of carnosine and anserine to CN1. CN1 comprises 2 chains (Chains A and B). Both monomers are found to work independently and alternatingly. The displacement of Zn2+ pair is found to disrupt the substrate binding. CN1 employs residues from the neighbour chain (H235, T335, and T337) to form the active site. This highlights the importance of a dimer for enzymatic activity. Anserine is more resistant to CN 1 than carnosine because of its bulky and dehydrated imidazole moiety. Although both dipeptides can direct the peptide oxygen to the active Zn2+ which can facilitate the catalytic reaction, the bulky methylated imidazole on anserine promotes various poses that can retard the hydrolytic activity in contrast to carnosine. Anserine is likely to be the temporary competitive inhibitor by retarding the carnosine catabolism.

N-Benzoylthiourea-pyrrolidine carboxylic acid derivatives bearing an imidazole moiety: Synthesis, characterization, crystal structure, in vitro ChEs inhibition, and antituberculosis, antibacterial, antifungal studies

A series of novel N-benzoylthiourea-pyrrolidine carboxylic acid derivatives bearing an imidazole moiety has been prepared and their various biological activities are evaluated. The ability of forming intermolecular hydrogen-bonds of these molecules was pursued in the search of the best antimicrobial activity. The synthesized compounds were tested to search whether they had an enzyme inhibitory potency against AChE and BChE, which are the main targets for Alzheimer's disease. The prepared compounds were also screened for antituberculosis activity against M. tuberculosis H37Rv strain and the antibacterial activity against E. coli, A. baumannii, S. aureus, B. subtilis, A. hydrophila, bacteria. In addition, their antifungal activities are also evaluated against C. tropicalis, C. albicans, C. glabrata strains.