Displaying publications 81 - 100 of 273 in total

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  1. Molecular interactions of trichoderma β-1,4-glucosidase (ThBglT12) with mycelial cell wall components of phytopathogenic Macrophomina phaseolina
    Mohammad Hood MH, Tengku Abdul Hamid TH, Abdul Wahab RA, Huyop FZ, Kaya Y, Abdul Hamid AAA
    J Biomol Struct Dyn, 2023 Apr;41(7):2831-2847.
    PMID: 35174777 DOI: 10.1080/07391102.2022.2039772
    Efficacy of a β-1,4-glucosidase from Trichoderma harzianum T12 (ThBglT12) in disrupting the cell wall of the phytopathogenic fungus M. phaseolina (Macrophomina phaseolina) was studied, as the underlying molecular mechanisms of cell wall recognition remains elusive. In this study, the binding location identified by a consensus of residues predicted by COACH tool, blind docking, and multiple sequence alignment revealed that molecular recognition by ThBglT12 occurred through interactions between the α-1,3-glucan, β-1,3-glucan, β-1,3/1,4-glucan, and chitin components of M. phaseolina, with corresponding binding energies of -7.4, -7.6, -7.5 and -7.8 kcal/mol. The residue consensus verified the participation of Glu172, Tyr304, Trp345, Glu373, Glu430, and Trp431 in the active site pocket of ThBglT12 to bind the ligands, of which Trp345 was the common interacting residue. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), total energy, and minimum distance calculation from molecular dynamics (MD) simulation further confirmed the stability and the closeness of the binding ligands into the ThBglT12 active site pocket. The h-bond occupancy by Glu373 and Trp431 instated the role of the nucleophile for substrate recognition and specificity, crucial for cleaving the β-1,4 linkage. Further investigation showed that the proximity of Glu373 to the anomeric carbon of β-1,3/1,4-glucan (3.5 Å) and chitin (5.5 Å) indicates the nucleophiles' readiness to form enzyme-substrate intermediates. Plus, the neighboring water molecule appeared to be correctly positioned and oriented towards the anomeric carbon to hydrolyze the β-1,3/1,4-glucan and chitin, in less than 4.0 Å. In a nutshell, the study verified that the ThBglT12 is a good alternative fungicide to inhibit the growth of M. phaseolina.Communicated by Ramaswamy H. Sarma.
    Matched MeSH terms: Ligands
  2. Fulltext iPSC-derived cells lack immune tolerance to autologous NK-cells due to imbalance in ligands for activating and inhibitory NK-cell receptors
    Bogomiakova ME, Sekretova EK, Anufrieva KS, Khabarova PO, Kazakova AN, Bobrovsky PA, et al.
    Stem Cell Res Ther, 2023 Apr 11;14(1):77.
    PMID: 37038186 DOI: 10.1186/s13287-023-03308-5
    BACKGROUND: Dozens of transplants generated from pluripotent stem cells are currently in clinical trials. The creation of patient-specific iPSCs makes personalized therapy possible due to their main advantage of immunotolerance. However, some reports have claimed recently that aberrant gene expression followed by proteome alterations and neoantigen formation can result in iPSCs recognition by autologous T-cells. Meanwhile, the possibility of NK-cell activation has not been previously considered. This study focused on the comparison of autologous and allogeneic immune response to iPSC-derived cells and isogeneic parental somatic cells used for reprogramming.

    METHODS: We established an isogeneic cell model consisting of parental dermal fibroblasts, fibroblast-like iPSC-derivatives (iPS-fibro) and iPS-fibro lacking beta-2-microglobulin (B2M). Using the cells obtained from two patients, we analyzed the activation of autologous and allogeneic T-lymphocytes and NK-cells co-cultured with target cells.

    RESULTS: Here we report that cells differentiated from iPSCs can be recognized by NK-cells rather than by autologous T-cells. We observed that iPS-fibro elicited a high level of NK-cell degranulation and cytotoxicity, while isogeneic parental skin fibroblasts used to obtain iPSCs barely triggered an NK-cell response. iPSC-derivatives with B2M knockout did not cause an additional increase in NK-cell activation, although they were devoid of HLA-I, the major inhibitory molecules for NK-cells. Transcriptome analysis revealed a significant imbalance of ligands for activating and inhibitory NK-cell receptors in iPS-fibro. Compared to parental fibroblasts, iPSC-derivatives had a reduced expression of HLA-I simultaneously with an increased gene expression of major activating ligands, such as MICA, NECTIN2, and PVR. The lack of inhibitory signals might be due to insufficient maturity of cells differentiated from iPSCs. In addition, we showed that pretreatment of iPS-fibro with proinflammatory cytokine IFNγ restored the ligand imbalance, thereby reducing the degranulation and cytotoxicity of NK-cells.

    CONCLUSION: In summary, we showed that iPSC-derived cells can be sensitive to the cytotoxic potential of autologous NK-cells regardless of HLA-I status. Thus, the balance of ligands for NK-cell receptors should be considered prior to iPSC-based cell therapies. Trial registration Not applicable.

    Matched MeSH terms: Ligands
  3. Thiadiazole-, selenadiazole- and triazole-fused anthraquinones as G-quadruplex targeting anticancer compounds
    Andreeva DV, Vedekhina TS, Gostev AS, Dezhenkova LG, Volodina YL, Markova AA, et al.
    Eur J Med Chem, 2024 Mar 15;268:116222.
    PMID: 38387333 DOI: 10.1016/j.ejmech.2024.116222
    G-quadruplex (G4) ligands attract considerable attention as potential anticancer therapeutics. In this study we proposed an original scheme for synthesis of azole-fused anthraquinones and prepared a series of G4 ligands carrying amino- or guanidinoalkylamino side chains. The heterocyclic core and structure of the terminal groups strongly affect on binding to G4-forming oligonucleotides, cellular accumulation and antitumor potency of compounds. In particular, thiadiazole- and selenadiazole- but not triazole-based ligands inhibit the proliferation of tumor cells (e.g. K562 leukemia) and stabilize primarily telomeric and c-MYC G4s. Anthraselenadiazole derivative 11a showed a good affinity to c-MYC G4 in vitro and down-regulated expression of c-MYC oncogene in cellular conditions. Further studies revealed that anthraselenadiazole 11a provoked cell cycle arrest and apoptosis in a dose- and time-dependent manner inhibiting K562 cells growth. Taken together, this work gives a valuable example that the closely related heterocycles may cause a significant difference in biological properties of G4 ligands.
    Matched MeSH terms: Ligands
  4. Leveraging binding pose metadynamics to optimise target fishing predictions for three diverse ligands and their true targets
    Yau MQ, Wan AJ, Tiong ASH, Yiap YS, Loo JSE
    Chem Biol Drug Des, 2024 Jul;104(1):e14591.
    PMID: 39010276 DOI: 10.1111/cbdd.14591
    Computational target fishing plays an important role in target identification, particularly in drug discovery campaigns utilizing phenotypic screening. Numerous approaches exist to predict potential targets for a given ligand, but true targets may be inconsistently ranked. More advanced simulation methods may provide benefit in such cases by reranking these initial predictions. We evaluated the ability of binding pose metadynamics to improve the predicted rankings for three diverse ligands and their six true targets. Initial predictions using pharmacophore mapping showed no true targets ranked in the top 50 and two targets each ranked within the 50-100, 100-150, and 250-300 ranges respectively. Following binding pose metadynamics, ranking of true targets improved for four out of the six targets and included the highest ranked predictions overall, while rankings deteriorated for two targets. The revised rankings predicted two true targets ranked within the top 50, and one target each within the 50-100, 100-150, 150-200, and 200-250 ranges respectively. The findings of this study demonstrate that binding pose metadynamics may be of benefit in refining initial predictions from structure-based target fishing algorithms, thereby improving the efficiency of the target identification process in drug discovery efforts.
    Matched MeSH terms: Ligands
  5. Cu(II) complexes based on benzimidazole ligands: synthesis, characterization, DFT, molecular docking & bioactivity study
    Hamali MA, Roney M, Dubey A, Uddin MN, Zulkifli NA, Fasihi Mohd Aluwi MF, et al.
    Future Med Chem, 2024;16(23):2535-2546.
    PMID: 39530504 DOI: 10.1080/17568919.2024.2419353
    Aim: The biggest cause of cancer deaths globally was lung cancer. New cancer fighting drugs are needed due to the rising number of cancer patients and cancer cells' treatment resistance.Results: Two Cu(II) complexes, synthesized from ligands based on 2-aminomethyl benzimidazole and salicylaldehyde derivatives, were designed and evaluated for their effectiveness against A549 lung cancer. The compounds were subjected to computational calculation using Density Functional Theory (DFT) to gather information on their reactivity. Furthermore, molecular docking are utilized to simulate the interaction between the compound and the MPP-9 protein. The synthesis of the ligands and their Cu(II) metal complexes are efficient and straightforward. The complexation between copper atom and the ligand are in 1:1 ratio. The MTT assay of the compounds against A549 lung carcinoma reveals that the both Cu(II) complexes good cytotoxicity activity, in comparison to their respective ligands. The low HOMO-LUMO band gap based on the DFT calculation predicts the high reactivity of the compounds. Furthermore, the low binding energy and the numbers of interactions of the Cu(II) complexes with MMP-9 protein binding site coincide with the antiproliferative activity tested in vitro.Conclusion: The cytotoxicity studies performed for Cu(L1Br) are promising, indicating a good candidate for a future drug.
    Matched MeSH terms: Ligands
  6. Study of the antidiabetic mechanism of berberine compound on FOXO1 transcription factor through molecular docking and molecular dynamics simulations
    Maksum IP, Rustaman R, Deawati Y, Rukayadi Y, Utami AR, Nafisa ZK
    J Mol Model, 2024 Jul 09;30(8):260.
    PMID: 38981921 DOI: 10.1007/s00894-024-06060-6
    CONTEXT: Diabetes mellitus (DM) is a metabolic disorder disease that causes hyperglycemia conditions and associated with various chronic complications leading to mortality. Due to high toxicity of conventional diabetic drugs, the exploration of natural compounds as alternative diabetes treatments has been widely carried out. Previous in silico studies have highlighted berberine, a natural compound, as a promising alternative in antidiabetic therapy, potentially acting through various pathways, including the inhibition of the FOXO1 transcription factor in the gluconeogenesis pathway. However, the specific mechanism by which berberine interacts with FOXO1 remains unclear, and research in this area is relatively limited. Therefore, this study aims to determine the stability of berberine structure with FOXO1 based on RMSD, RMSF, binding energy, and trajectory analysis to determine the potential of berberine to inhibit the gluconeogenesis pathway. This research was conducted by in silico method with molecular docking using AutoDock4.2 and molecular dynamics study using Amber20, then visualized by VMD.

    METHODS: Docking between ligand and FOXO1 receptor was carried out with Autodock4.2. For molecular dynamics simulations, the force fields of DNA.OL15, protein.ff14SB, gaff2, and tip3p were used.

    Matched MeSH terms: Ligands
  7. N-substituted tetrahydro-beta-carboline as mu-opioid receptors ligands: in silico study; molecular docking, ADMET and molecular dynamics approach
    Alananzeh WA, Al-Qattan MN, Ayipo YO, Mordi MN
    Mol Divers, 2024 Jun;28(3):1273-1289.
    PMID: 37133710 DOI: 10.1007/s11030-023-10655-1
    Manipulating intracellular signals by interaction with transmembranal G-protein-coupled receptors (GPCRs) is the way of action of more than 30% of available medicines. Designing molecules against GPCRs is most challenging due to their flexible binding orthosteric and allosteric pockets, a property that lead to different mode and extent of activation of intracellular mediators. Here, in the current study we aimed to design N-substituted tetrahydro-beta-carbolines (THβC's) targeting Mu Opioid Receptors (MORs). We performed ligand docking study for reference and designed compounds against active and inactive states of MOR, as well as the active state bound to intracellular mediator of Gi. The reference compounds include 40 known agonists and antagonists, while the designed compounds include 25,227 N-substituted THβC analogues. Out of the designed compounds, 15 compounds were comparatively having better extra precision (XP) Gscore and were analyzed for absorption, distribution, metabolism, and excretion-toxicity (ADMET) properties, drug-likness, and molecular dynamic (MD) simulation. The results showed that N-substituted tetrahydro-beta-carbolines with and without C6-methoxy group substitutions (THBC/6MTHBC) analogues of A1/B1 and A9/B9 have relatively acceptable affinity and within pocket-stability toward MOR compared to the reference compounds of morphine (agonist) and naloxone (antagonist). Moreover, the designed analogues interact with key residue within the binding pocket of Asp 147 that is reported to be involved in receptor activation. In conclusion, the designed THBC analogues represent a good starting point for designing opioid receptor ligands other than morphinan scaffold, that have good synthetic accessibility which promotes feasible structural manipulation to tailor pharmacological effects with minimal side effects.
    Matched MeSH terms: Ligands
  8. Evaluating ligand-receptor networks of TGF-beta with membrane computing
    Muniyandi RC, Zin AM
    Pak J Biol Sci, 2011 Dec 15;14(24):1100-8.
    PMID: 22335049
    Ligand-Receptor Networks of TGF-beta plays essential role in transmitting a wide range of extracellular signals that affect many cellular processes such as cell growth. However, the modeling of these networks with conventional approach such as ordinary differential equations has not taken into account, the spatial structure and stochastic behavior of processes involve in these networks. Membrane computing as the alternatives approach provides spatial structure for molecular computation in which processes are evaluated in a non-deterministic and maximally parallel way. This study is carried out to evaluate the membrane computing model of Ligand-Receptor Networks of TGF-beta with model checking approach. The results show that membrane computing model has sustained the behaviors and properties of Ligand-Receptor Networks of TGF-beta. This reinforce that membrane computing is capable in analyzing processes and behaviors in hierarchical structure of cell such as Ligand-Receptor Networks of TGF-beta better than the deterministic approach of conventional mathematical models.
    Matched MeSH terms: Ligands*
  9. Fulltext Ligand-based virtual screening using Bayesian inference network and reweighted fragments
    Ahmed A, Abdo A, Salim N
    ScientificWorldJournal, 2012;2012:410914.
    PMID: 22623895 DOI: 10.1100/2012/410914
    Many of the similarity-based virtual screening approaches assume that molecular fragments that are not related to the biological activity carry the same weight as the important ones. This was the reason that led to the use of Bayesian networks as an alternative to existing tools for similarity-based virtual screening. In our recent work, the retrieval performance of the Bayesian inference network (BIN) was observed to improve significantly when molecular fragments were reweighted using the relevance feedback information. In this paper, a set of active reference structures were used to reweight the fragments in the reference structure. In this approach, higher weights were assigned to those fragments that occur more frequently in the set of active reference structures while others were penalized. Simulated virtual screening experiments with MDL Drug Data Report datasets showed that the proposed approach significantly improved the retrieval effectiveness of ligand-based virtual screening, especially when the active molecules being sought had a high degree of structural heterogeneity.
    Matched MeSH terms: Ligands*
  10. Fulltext Delivery of chimeric hepatitis B core particles into liver cells
    Lee KW, Tey BT, Ho KL, Tan WS
    J Appl Microbiol, 2012 Jan;112(1):119-31.
    PMID: 21992228 DOI: 10.1111/j.1365-2672.2011.05176.x
    To display a liver-specific ligand on the hepatitis B virus core particles for cell-targeting delivery.
    Matched MeSH terms: Ligands*
  11. A molecular dynamics study of Beta-Glucosidase B upon small substrate binding
    Mazlan NS, Ahmad Khairudin NB
    J Biomol Struct Dyn, 2016 Jul;34(7):1486-94.
    PMID: 26261863 DOI: 10.1080/07391102.2015.1081570
    Paenibacillus polymyxa β-glucosidase B (BglB), belongs to a GH family 1, is a monomeric enzyme that acts as an exo-β-glucosidase hydrolysing cellobiose and cellodextrins of higher degree of polymerization using retaining mechanism. A molecular dynamics (MD) simulation was performed at 300 K under periodic boundary condition for 5 ns using the complexes structure obtained from previous docking study, namely BglB-Beta-d-glucose and BglB-Cellobiose. From the root-mean-square deviation analysis, both enzyme complexes were reported to deviate from the initial structure in the early part of the simulation but it was stable afterwards. The root-mean-square fluctuation analysis revealed that the most flexible regions comprised of the residues from 26 to 29, 43 to 53, 272 to 276, 306 to 325 and 364 to 367. The radius of gyration analysis had shown the structure of BglB without substrate became more compact towards the end of the simulation compare to other two complexes. The residues His122 and Trp410 were observed to form stable hydrogen bond with occupancy higher than 10%. In conclusion, the behaviour of BglB enzyme towards the substrate binding was successfully explored via MD simulation approaches.
    Matched MeSH terms: Ligands*
  12. Fulltext Binding Affinity of a Highly Sensitive Au/Ag/Au/Chitosan-Graphene Oxide Sensor Based on Direct Detection of Pb2+and Hg2+Ions
    Kamaruddin NH, Bakar AAA, Mobarak NN, Zan MSD, Arsad N
    Sensors (Basel), 2017 Oct 06;17(10).
    PMID: 28984826 DOI: 10.3390/s17102277
    The study of binding affinity is essential in surface plasmon resonance (SPR) sensing because it allows researchers to quantify the affinity between the analyte and immobilised ligands of an SPR sensor. In this study, we demonstrate the derivation of the binding affinity constant, K, for Pb2+and Hg2+ions according to their SPR response using a gold/silver/gold/chitosan-graphene oxide (Au/Ag/Au/CS-GO) sensor for the concentration range of 0.1-5 ppm. The higher affinity of Pb2+to binding with the CS-GO sensor explains the outstanding sensitivity of 2.05 °ppm-1against 1.66 °ppm-1of Hg2+. The maximum signal-to-noise ratio (SNR) upon detection of Pb2+is 1.53, and exceeds the suggested logical criterion of an SNR. The Au/Ag/Au/CS-GO SPR sensor also exhibits excellent repeatability in Pb2+due to the strong bond between its functional groups and this cation. The adsorption data of Pb2+and Hg2+on the CS-GO sensor fits well with the Langmuir isotherm model where the affinity constant, K, of Pb2+and Hg2+ions is computed. The affinity of Pb2+ions to the Au/Ag/Au/CS-GO sensor is significantly higher than that of Hg2+based on the value of K, 7 × 10⁵ M-1and 4 × 10⁵ M-1, respectively. The higher shift in SPR angles due to Pb2+and Hg2+compared to Cr3+, Cu2+and Zn2+ions also reveals the greater affinity of the CS-GO SPR sensor to them, thus supporting the rationale for obtaining K for these two heavy metals. This study provides a better understanding on the sensing performance of such sensors in detecting heavy metal ions.
    Matched MeSH terms: Ligands
  13. Pharmacophore Based Virtual Screening Approach to Identify Selective PDE4B Inhibitors
    Gaurav A, Gautam V
    Iran J Pharm Res, 2017;16(3):910-923.
    PMID: 29201082
    Phosphodiesterase 4 (PDE4) has been established as a promising target in asthma and chronic obstructive pulmonary disease. PDE4B subtype selective inhibitors are known to reduce the dose limiting adverse effect associated with non-selective PDE4B inhibitors. This makes the development of PDE4B subtype selective inhibitors a desirable research goal. To achieve this goal, ligand based pharmacophore modeling approach is employed. Separate pharmacophore hypotheses for PDE4B and PDE4D inhibitors were generated using HypoGen algorithm and 106 PDE4 inhibitors from literature having thiopyrano [3,2-d] Pyrimidines, 2-arylpyrimidines, and triazines skeleton. Suitable training and test sets were created using the molecules as per the guidelines available for HypoGen program. Training set was used for hypothesis development while test set was used for validation purpose. Fisher validation was also used to test the significance of the developed hypothesis. The validated pharmacophore hypotheses for PDE4B and PDE4D inhibitors were used in sequential virtual screening of zinc database of drug like molecules to identify selective PDE4B inhibitors. The hits were screened for their estimated activity and fit value. The top hit was subjected to docking into the active sites of PDE4B and PDE4D to confirm its selectivity for PDE4B. The hits are proposed to be evaluated further using in-vitro assays.
    Matched MeSH terms: Ligands
  14. Recent advances in galactose-engineered nanocarriers for the site-specific delivery of siRNA and anticancer drugs
    Jain A, Jain A, Parajuli P, Mishra V, Ghoshal G, Singh B, et al.
    Drug Discov Today, 2018 05;23(5):960-973.
    PMID: 29129804 DOI: 10.1016/j.drudis.2017.11.003
    Galactosylated nanocarriers have recently emerged as viable and versatile tools to deliver drugs at an optimal rate specifically to their target tissues or cells, thus maximizing their therapeutic benefits while circumventing off-target effects. The abundance of lectin receptors on cell surfaces makes the galactosylated carriers suitable for the targeted delivery of bioactives. Additionally, tethering of galactose (GAL) to various carriers, including micelles, liposomes, and nanoparticles (NPs), might also be appropriate for drug delivery. Here, we review recent advances in the development of galactosylated nanocarriers for active tumor targeting. We also provide a brief overview of the targeting mechanisms and cell receptor theory involved in the ligand-receptor-mediated delivery of drug carriers.
    Matched MeSH terms: Ligands
  15. Fulltext Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer's disease
    Abbasi MA, Hassan M, Aziz-Ur-Rehman, Siddiqui SZ, Shah SAA, Raza H, et al.
    PeerJ, 2018;6:e4962.
    PMID: 29967717 DOI: 10.7717/peerj.4962
    The present study comprises the synthesis of a new series of sulfonamides derived from 4-methoxyphenethylamine (1). The synthesis was initiated by the reaction of 1 with 4-methylbenzenesulfonyl chloride (2) in aqueous sodium carbonate solution at pH 9 to yield N-(4-methoxyphenethyl)-4-methylbenzensulfonamide (3).This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides, (4a-j), using N,N-dimethylformamide (DMF) as solvent and LiH as activator to produce a series of new N-(4-methoxyphenethyl)-N-(substituted)-4-methylbenzenesulfonamides (5a-j). The structural characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. The elemental analysis data was also coherent with spectral data of these molecules. The inhibitory effects on acetylcholinesterase and DPPH were evaluated and it was observed that N-(4-Methoxyphenethyl)-4-methyl-N-(2-propyl)benzensulfonamide (5c) showed acetylcholinesterase inhibitory activity 0.075 ± 0.001 (IC50 0.075 ± 0.001 µM) comparable to Neostigmine methylsulfate (IC50 2.038 ± 0.039 µM).The docking studies of synthesized ligands 5a-j were also carried out against acetylcholinesterase (PDBID 4PQE) to compare the binding affinities with IC50 values. The kinetic mechanism analyzed by Lineweaver-Burk plots demonstrated that compound (5c) inhibits the acetylcholinesterase competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (5c) is 2.5 µM. It was also found from kinetic analysis that derivative 5c irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound 5c may serve as lead structure for the design of more potent acetylcholinesterase inhibitors.
    Matched MeSH terms: Ligands
  16. Fulltext Analysis of the Binding of Aripiprazole to Human Serum Albumin: The Importance of a Chloro-Group in the Chemical Structure
    Sakurama K, Kawai A, Tuan Giam Chuang V, Kanamori Y, Osa M, Taguchi K, et al.
    ACS Omega, 2018 Oct 31;3(10):13790-13797.
    PMID: 30411049 DOI: 10.1021/acsomega.8b02057
    Aripiprazole (ARP), a quinolinone derivative, is an atypical antipsychotic drug that is used in the treatment of schizophrenia. ARP has an extensive distribution and more than 99% of the ARP and dehydro-ARP, the main active metabolite, is bound to plasma proteins. However, information regarding the protein binding of ARP is limited. In this study, we report on a systematic study of the protein binding of ARP. The interaction of ARP and structurally related compounds with human serum albumin (HSA) was examined using equilibrium dialysis, circular dichroism (CD) spectroscopy, fluorescent probe displacement, and an X-ray crystallographic analysis. The binding affinities (nK) for ARP and its main metabolite, dehydro-ARP with HSA were found to be significantly higher than other structurally related compounds. The results of equilibrium dialysis experiments and CD spectral data indicated that the chloro-group linked to the phenylpiperazine ring in the ARP molecule plays a major role in the binding of these ligands to HSA. Furthermore, fluorescent probe displacement results indicated that ARP appears to bind at the site II pocket in subdomain III. A detailed CD spectral analysis suggests that the chloro-group linked to the phenylpiperazine ring may control the geometry of the ARP molecule when binding in the site II binding pocket. X-ray crystallographic analysis of the ARP-HSA complex revealed that the distance between the chlorine atom at the 3-positon of dichlorophenyl-piperazine on ARP and the sulfur atom of Cys392 in HSA was 3.4-3.6 Å. A similar halogen bond interaction has also been observed in the HSA structure complexed with diazepam, which also contains a chloro-group. Thus, the mechanism responsible for the binding of ARP to a protein elucidated here should be relevant for assessing the pharmacokinetics and pharmacodynamics of ARP in various clinical situations and for designing new drugs.
    Matched MeSH terms: Ligands
  17. Flurbiprofen derivatives as novel α-amylase inhibitors: Biology-oriented drug synthesis (BIODS), in vitro, and in silico evaluation
    Khan M, Alam A, Khan KM, Salar U, Chigurupati S, Wadood A, et al.
    Bioorg Chem, 2018 12;81:157-167.
    PMID: 30125730 DOI: 10.1016/j.bioorg.2018.07.038
    Novel derivatives of flurbiprofen 1-18 including flurbiprofen hydrazide 1, substituted aroyl hydrazides 2-9, 2-mercapto oxadiazole derivative 10, phenacyl substituted 2-mercapto oxadiazole derivatives 11-15, and benzyl substituted 2-mercapto oxadiazole derivatives 16-18 were synthesized and characterized by EI-MS, 1H and 13C NMR spectroscopic techniques. All derivatives 1-18 were screened for α-amylase inhibitory activity and demonstrated a varying degree of potential ranging from IC50 = 1.04 ± 0.3 to 2.41 ± 0.09 µM as compared to the standard acarbose (IC50 = 0.9 ± 0.04 µM). Out of eighteen compounds, derivatives 2 (IC50 = 1.69 ± 0.1 µM), 3 (IC50 = 1.04 ± 0.3 µM), 9 (IC50 = 1.25 ± 1.05 µM), and 13 (IC50 = 1.6 ± 0.18 µM) found to be excellent inhibitors while rest of the compounds demonstrated comparable inhibition potential. A limited structure-activity relationship (SAR) was established by looking at the varying structural features of the library. In addition to that, in silico study was conducted to understand the binding interactions of the compounds (ligands) with the active site of α-amylase enzyme.
    Matched MeSH terms: Ligands
  18. Ion-Imprinted Polymer for Selective Separation of Cerium(III) Ions from Rare Earth Mixture
    Rahman ML, Puah PY, Sarjadi MS, Arshad SE, Musta B, Sarkar SM
    J Nanosci Nanotechnol, 2019 09 01;19(9):5796-5802.
    PMID: 30961741 DOI: 10.1166/jnn.2019.16538
    Ion-imprinting polymers (IIPs) materials draw the great recognition because of the powerful selectivity to the desired metal ions. Therefore, the ion-imprinting polymer (Ce-IIP) was prepared by using cerium metal with amidoxime ligand as the complexing agent, in addition ethylene glycol dimethacrylate (EGDMA) and 2,2-azobisisobutyronitrile (AIBN) are crosslinking agent and free radical initiator, respectively. Aqueous HCl was applied to leach the cerium ions from the imprinted polymer for the creation of cavities of template, which is utilized for further cerium ions adsorption with high selectivity. The Ce-IIP was characterized by using ICP-MS, FE-SEM and also solid state analysis by UV-vis NIR spectroscopy. FT-IR study confirmed the complexation of the Ce-IIP was successful. The optimum pH was found to be 6 and the highest adsorption capacity was estimated about 145 mg g-1. Thus, the prepared Ce-IIP gave very good selectivity to cerium ions in the presence of lanthanide ions and also Ce-IIP can be reused 10 times without a substantial loss in adsorption capacity.
    Matched MeSH terms: Ligands
  19. A novel ruthenium-tungsten bimetallic complex dye-sensitizer for photoelectrochemical cells application
    Khuzaimah Arifin, Wan Ramli Wan Daud, Mohammad B. Kassim
    Sains Malaysiana, 2014;43:95-101.
    A novel bimetallic double thiocyanate-bridged ruthenium and tungsten metal complex containing bipyridyl and dithiolene co-ligands was synthesized and the behavior of the complex as a dye-sensitizer for a photoelectrochemical (PEG) cell for a direct water splitting reaction was investigated. The ligands and metal complexes were characterized on the basis of elemental analysis as well as uv-Vis, Fourier transform infrared ( Pim) and nuclear magnetic resonance (11I and 13C NMR) spectroscopy. Cyclic voltammetry of the bimetallic complex showed multiple redox couples, in which half potentials E 112 at 0 .625 , 0.05 and 0.61 V were assigned as the formal redox processes of Ru(III)IRu(II) reduction, W(IV)IW(V) and W(V)IW(VI) oxidations, respectively. Photocurrent measurements were performed in homogeneous system and TiO2 was used as the photoanode for photocurrent measurements. Current density generated by the bimetallic complex was higher than that of N3 commercial dye which suggested that the bimetallic complex donated more electrons to the semiconductor.
    Matched MeSH terms: Ligands
  20. Fulltext Synthesis, biological activity and molecular docking of new tricyclic series as α-glucosidase inhibitors
    Abuelizz HA, Iwana NANI, Ahmad R, Anouar EH, Marzouk M, Al-Salahi R
    BMC Chem, 2019 Dec;13(1):52.
    PMID: 31384800 DOI: 10.1186/s13065-019-0560-4
    Diabetes is an emerging metabolic disorder. α-Glucosidase inhibitors, such as acarbose, delay the hydrolysis of carbohydrates by interfering with the digestive enzymes. This action decreases the glucose absorption and the postprandial glucose level. We have synthesized 25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids and evaluated their α-glucosidase inhibitory activity. Compounds 6h and 6d have shown stronger activity than that of acarbose. Compound 6h exhibited the highest inhibition with an IC50 of 104.07 µM. Molecular modelling studies revealed that compound 6h inhibits α-glucosidase due to the formation of a stable ligand-α-glucosidase complex and extra hydrogen bond interactions, and directed in the binding site by Trp329.25 tricyclic 2-phenoxypyrido[3,2-e][1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-ones hybrids have been synthesized and evaluated their α-glucosidase inhibitory activity. Compounds 6h have shown stronger activity than that of acarbose.
    Matched MeSH terms: Ligands
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