Displaying publications 161 - 180 of 634 in total

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  1. AgNO3 dependant modulation of glucose mediated respiration kinetics in Escherichia coli at different pH and temperature
    Afiqah RN, Paital B, Kumar S, Majeed AB, Tripathy M
    J. Mol. Recognit., 2016 11;29(11):544-554.
    PMID: 27406464 DOI: 10.1002/jmr.2554
    The inhibitory role of AgNO3 on glucose-mediated respiration in Escherichia coli has been investigated as a function of pH and temperature using Clark-type electrode, environmental scanning electron microscopy, and computational tools. In the given concentration of bacterial suspension (1 × 10(8)  CFU/ml), E. coli showed an increasing nonlinear trend of tetra-phasic respiration between 1-133 μM glucose concentration within 20 min. The glucose concentrations above 133 μM did not result any linear increment in respiration but rather showed a partial inhibition at higher glucose concentrations (266-1066 μM). In the presence of glucose, AgNO3 caused a concentration-dependent (47-1960 μM) inhibition of the respiration rate within 4 min of its addition. The respiration rate was the highest at pH 7-8 and then was decreased on either side of this pH range. The inhibitory action of AgNO3 upon bacterial respiration was the highest at 37 °C. The observations of the respiration data were well supported by the altered bacterial morphology as observed in electron microscopic study. Docking study indicated the AgNO3 binding to different amino acids of all respiratory complex enzymes in E. coli and thereby explaining its interference with the respiratory chain. Copyright © 2016 John Wiley & Sons, Ltd.
    Matched MeSH terms: Molecular Docking Simulation
  2. In silico binding analysis and SAR elucidations of newly designed benzopyrazine analogs as potent inhibitors of thymidine phosphorylase
    Taha M, Ismail NH, Imran S, Rahim F, Wadood A, Al Muqarrabun LM, et al.
    Bioorg Chem, 2016 10;68:80-9.
    PMID: 27474803 DOI: 10.1016/j.bioorg.2016.07.010
    Thymidine phosphorylase (TP) is up regulated in wide variety of solid tumors and therefore presents a remarkable target for drug discovery in cancer. A novel class of extremely potent TPase inhibitors based on benzopyrazine (1-28) has been developed and evaluated against thymidine phosphorylase enzyme. Out of these twenty-eight analogs eleven (11) compounds 1, 4, 14, 15, 16, 17, 18, 19, 20, 24 and 28 showed potent thymidine phosphorylase inhibitory potentials with IC50 values ranged between 3.20±0.30 and 37.60±1.15μM when compared with the standard 7-Deazaxanthine (IC50=38.68±4.42μM). Structure-activity relationship was established and molecular docking studies were performed to determine the binding interactions of these newly synthesized compounds. Current studies have revealed that these compounds established stronger hydrogen bonding networks with active site residues as compare to the standard compound 7DX.
    Matched MeSH terms: Molecular Docking Simulation
  3. Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies
    Taha M, Ismail NH, Ali M, Rashid U, Imran S, Uddin N, et al.
    Bioorg Chem, 2017 04;71:192-200.
    PMID: 28228228 DOI: 10.1016/j.bioorg.2017.02.005
    The high potential of quinoline containing natural products and their derivatives in medicinal chemistry led us to discover a novel series of compounds 6-23 based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal potential. The most potent compound (23, IC50=0.10±0.001μM) among the series was found ∼70 times more lethal than the standard drug. The current series 6-23 conceded in the development of fourteen (14) extraordinarily active compounds against leishmaniasis. In silico analysis were also performed to probe the mode of action while all the compounds structure were established by NMR and Mass spectral analysis.
    Matched MeSH terms: Molecular Docking Simulation
  4. Synthesis and study of anti-HIV-1 RT activity of 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives
    Chander S, Tang CR, Al-Maqtari HM, Jamalis J, Penta A, Hadda TB, et al.
    Bioorg Chem, 2017 06;72:74-79.
    PMID: 28371664 DOI: 10.1016/j.bioorg.2017.03.013
    In the present study, a series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were designed, synthesized and characterized by appropriate spectral analysis. Further, titled compounds were in-vitro screened against wild HIV-1 RT enzyme using ELISA based colorimetric assay, in which four compounds significantly inhibited the RT activity with IC50≤25µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC50 values 8.62 and 6.87µM respectively, during the in-vitro assay. Structure Activity Relationship (SAR) studies were performed for the synthesized compounds in order to estimate the effect of substitution pattern on the RT inhibitory potency. The cytotoxicity of the synthesized compounds was evaluated against T lymphocytes. Further, putative binding modes of the significantly active (A11) and the least active (A4) compounds with wild HIV-1 RT were also investigated using docking studies.
    Matched MeSH terms: Molecular Docking Simulation
  5. Experimental and computational approaches to reveal the potential of Ficus deltoidea leaves extract as α-amylase inhibitor
    Abu Bakar AR, Manaharan T, Merican AF, Mohamad SB
    Nat Prod Res, 2018 Feb;32(4):473-476.
    PMID: 28391727 DOI: 10.1080/14786419.2017.1312393
    Ficus deltoidea leaves extract are known to have good therapeutic properties such as antioxidant, anti-inflammatory and anti-diabetic. We showed that 50% ethanol-water extract of F. deltoidea leaves and its pungent compounds vitexin and isovitexin exhibited significant (p molecular docking analysis confirmed that vitexin has a higher binding affinity (-7.54 kcal/mol) towards α-amylase compared to isovitexin (-5.61 kcal/mol). On the other hand, the molecular dynamics findings showed that vitexin-α-amylase complex is more stable during the simulation of 20 ns when compared to the isovitexin-α-amylase complex. Our results suggest that vitexin is more potent and stable against α-amylase enzyme, thus it could develop as a therapeutic drug for the treatment of diabetes.
    Matched MeSH terms: Molecular Docking Simulation
  6. Biology-oriented drug synthesis (BIODS): In vitro β-glucuronidase inhibitory and in silico studies on 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives
    Salar U, Khan KM, Taha M, Ismail NH, Ali B, Qurat-Ul-Ain, et al.
    Eur J Med Chem, 2017 Jan 05;125:1289-1299.
    PMID: 27886546 DOI: 10.1016/j.ejmech.2016.11.031
    Current study is based on the biology-oriented drug synthesis (BIODS) of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl carboxylate derivatives 1-26, by treating metronidazole with different aryl and hetero-aryl carboxylic acids in the presence of 1,1'-carbonyl diimidazole (CDI) as a coupling agent. Structures of all synthetic derivatives were confirmed with the help of various spectroscopic techniques such as EI-MS, (1)H -NMR and (13)C NMR. CHN elemental analyses were also found in agreement with the calculated values. Synthetic derivatives were evaluated to check their β-glucuronidase inhibitory activity which revealed that except few derivatives, all demonstrated good inhibition in the range of IC50 = 1.20 ± 0.01-60.30 ± 1.40 μM as compared to the standard d-saccharic acid 1,4-lactone (IC50 = 48.38 ± 1.05 μM). Compounds 1, 3, 4, 6, 9-19, and 21-24 were found to be potent analogs and showed superior activity than standard. Limited structure-activity relationship is suggested that the molecules having electron withdrawing groups like NO2, F, Cl, and Br, were displayed better activity than the compounds with electron donating groups such as Me, OMe and BuO. To verify these interpretations, in silico study was also performed, a good correlation was observed between bioactivities and docking studies.
    Matched MeSH terms: Molecular Docking Simulation
  7. Ethyl nitrobenzoate: A novel scaffold for cholinesterase inhibition
    Yeong KY, Liew WL, Murugaiyah V, Ang CW, Osman H, Tan SC
    Bioorg Chem, 2017 02;70:27-33.
    PMID: 27863748 DOI: 10.1016/j.bioorg.2016.11.005
    A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease.
    Matched MeSH terms: Molecular Docking Simulation
  8. Rational design of bis-indolylmethane-oxadiazole hybrids as inhibitors of thymidine phosphorylase
    Taha M, Rashid U, Imran S, Ali M
    Bioorg Med Chem, 2018 07 23;26(12):3654-3663.
    PMID: 29853339 DOI: 10.1016/j.bmc.2018.05.046
    Inhibition of Thymidine phosphorylase (TP) is continuously studied for the design and development of new drugs for the treatment of neoplastic diseases. As a part of our effort to identify TP inhibitors, we performed a structure-based virtual screening (SBVS) of our compound collection. Based on the insights gained from structures of virtual screening hits, a scaffold was designed using 1,3,4-oxadiazole as the basic structural feature and SAR studies were carried out for the optimization of this scaffold. Twenty-five novel bis-indole linked 1,3,4-oxadiazoles (7-31) were designed, synthesized and tested in vitro against E. coli TP (EcTP). Compound 7 emerged as potent TP inhibitor with an IC50 value of 3.50 ± 0.01 μM. Docking studies were carried out using GOLD software on thymidine phosphorylase from human (hTP) and E. coli (EcTP). Various hydrogen bonding, hydrophobic interactions, and π-π stacking were observed between designed molecules and the active site amino acid residues of the studied enzymes.
    Matched MeSH terms: Molecular Docking Simulation
  9. Norditerpenoid alkaloids of Delphinium denudatum as cholinesterase inhibitors
    Ahmad H, Ahmad S, Ali M, Latif A, Shah SAA, Naz H, et al.
    Bioorg Chem, 2018 08;78:427-435.
    PMID: 29698893 DOI: 10.1016/j.bioorg.2018.04.008
    Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.
    Matched MeSH terms: Molecular Docking Simulation
  10. Novel furan-containing peptide-based inhibitors of protein arginine deiminase type IV (PAD4)
    Teo CY, Tejo BA, Leow ATC, Salleh AB, Abdul Rahman MB
    Chem Biol Drug Des, 2017 Dec;90(6):1134-1146.
    PMID: 28581157 DOI: 10.1111/cbdd.13033
    Protein arginine deiminase type IV (PAD4) is responsible for the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullinated protein is the autoantigen in rheumatoid arthritis, and therefore, PAD4 is currently a promising therapeutic target for the disease. Recently, we reported the importance of the furan ring in the structure of PAD4 inhibitors. In this study, the furan ring was incorporated into peptides to act as the "warhead" of the inhibitors for PAD4. IC50 studies showed that the furan-containing peptide-based inhibitors were able to inhibit PAD4 to a better extent than the furan-containing small molecules that were previously reported. The best peptide-based inhibitor inhibited PAD4 reversibly and competitively with an IC50 value of 243.2 ± 2.4 μm. NMR spectroscopy and NMR-restrained molecular dynamic simulations revealed that the peptide-based inhibitor had a random structure. Molecular docking studies showed that the peptide-based inhibitor entered the binding site and interacted with the essential amino acids involved in the catalytic activity. The peptide-based inhibitor could be further developed into a therapeutic drug for rheumatoid arthritis.
    Matched MeSH terms: Molecular Docking Simulation
  11. Synthesis, in vitro and in silico studies of novel potent urease inhibitors: N-[4-({5-[(3-Un/substituted-anilino-3-oxopropyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1,3-thiazol-2-yl]benzamides
    Abbasi MA, Hassan M, Aziz-Ur-Rehman, Siddiqui SZ, Raza H, Shah SAA, et al.
    Bioorg Med Chem, 2018 07 30;26(13):3791-3804.
    PMID: 29903414 DOI: 10.1016/j.bmc.2018.06.005
    The present article describes the synthesis, in vitro urease inhibition and in silico molecular docking studies of a novel series of bi-heterocyclic bi-amides. The synthesis of title compounds was initiated by benzoylation, with benzoyl chloride (1), of the key starter ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (2) in weak basic aqueous medium followed by hydrazide formation, 4, and cyclization with CS2 to reach the parent bi-heterocyclic nucleophile, N-{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-1,3-thiazol-2-yl}benzamide (5). Various electrophiles, 8a-l, were synthesized by a two-step process and these were finally coupled with 5 to yield the targeted bi-heterocyclic bi-amide molecules, 9a-l. The structures of the newly synthesized products were corroborated by IR, 1H NMR, 13C NMR, EI-MS and elemental analysis. The in vitro screening of these molecules against urease explored that most of the compounds exhibit potent inhibitory potential against this enzyme. The compound 9j, with IC50 value of 2.58 ± 0.02 µM, exhibited most promising inhibitory activity among the series, relative to standard thiourea having IC50 value of 21.11 ± 0.12 µM. In silico studies fully augmented the experimental enzyme inhibition results. Chemo-informatics analysis showed that synthesized compounds (9a-l) mostly obeyed the Lipinski's rule. Molecular docking study suggested that ligand 9j exhibited good binding energy value (-7.10 kcal/mol) and binds within the active region of target protein. So, on the basis of present investigation, it was inferred that 9j may serve as a novel scaffold for designing more potent urease inhibitors.
    Matched MeSH terms: Molecular Docking Simulation
  12. Insight into the molecular mechanism of P-glycoprotein mediated drug toxicity induced by bioflavonoids: an integrated computational approach
    Wongrattanakamon P, Lee VS, Nimmanpipug P, Sirithunyalug B, Chansakaow S, Jiranusornkul S
    Toxicol. Mech. Methods, 2017 May;27(4):253-271.
    PMID: 27996361 DOI: 10.1080/15376516.2016.1273428
    In this work, molecular docking, pharmacophore modeling and molecular dynamics (MD) simulation were rendered for the mouse P-glycoprotein (P-gp) (code: 4Q9H) and bioflavonoids; amorphigenin, chrysin, epigallocatechin, formononetin and rotenone including a positive control; verapamil to identify protein-ligand interaction features including binding affinities, interaction characteristics, hot-spot amino acid residues and complex stabilities. These flavonoids occupied the same binding site with high binding affinities and shared the same key residues for their binding interactions and the binding region of the flavonoids was revealed that overlapped the ATP binding region with hydrophobic and hydrophilic interactions suggesting a competitive inhibition mechanism of the compounds. Root mean square deviations (RMSDs) analysis of MD trajectories of the protein-ligand complexes and NBD2 residues, and ligands pointed out these residues were stable throughout the duration of MD simulations. Thus, the applied preliminary structure-based molecular modeling approach of interactions between NBD2 and flavonoids may be gainful to realize the intimate inhibition mechanism of P-gp at NBD2 level and on the basis of the obtained data, it can be concluded that these bioflavonoids have the potential to cause herb-drug interactions or be used as lead molecules for the inhibition of P-gp (as anti-multidrug resistance agents) via the NBD2 blocking mechanism in future.
    Matched MeSH terms: Molecular Docking Simulation
  13. Fulltext Novel biphenyl ester derivatives as tyrosinase inhibitors: Synthesis, crystallographic, spectral analysis and molecular docking studies
    Kwong HC, Chidan Kumar CS, Mah SH, Chia TS, Quah CK, Loh ZH, et al.
    PLoS One, 2017;12(2):e0170117.
    PMID: 28241010 DOI: 10.1371/journal.pone.0170117
    Biphenyl-based compounds are clinically important for the treatments of hypertension and inflammatory, while many more are under development for pharmaceutical uses. In the present study, a series of 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl benzoates, 2(a-q), and 2-([1,1'-biphenyl]-4-yl)-2-oxoethyl pyridinecarboxylate, 2(r-s) were synthesized by reacting 1-([1,1'-biphenyl]-4-yl)-2-bromoethan-1-one with various carboxylic acids using potassium carbonate in dimethylformamide at ambient temperature. Single-crystal X-ray diffraction studies revealed a more closely packed crystal structure can be produced by introduction of biphenyl moiety. Five of the compounds among the reported series exhibited significant anti-tyrosinase activities, in which 2p, 2r and 2s displayed good inhibitions which are comparable to standard inhibitor kojic acid at concentrations of 100 and 250 μg/mL. The inhibitory effects of these active compounds were further confirmed by computational molecular docking studies and the results revealed the primary binding site is active-site entrance instead of inner copper binding site which acted as the secondary binding site.
    Matched MeSH terms: Molecular Docking Simulation
  14. Synthesis, molecular docking studies of hybrid benzimidazole as α-glucosidase inhibitor
    Zawawi NK, Taha M, Ahmat N, Ismail NH, Wadood A, Rahim F
    Bioorg Chem, 2017 02;70:184-191.
    PMID: 28043716 DOI: 10.1016/j.bioorg.2016.12.009
    Thiourea derivatives having benzimidazole 1-17 have been synthesized, characterized by 1H NMR, 13C NMR and EI-MS and evaluated for α-glucosidase inhibition. Identification of potential α-glucosidase inhibitors were done by in vitro screening of 17 thiourea bearing benzimidazole derivatives using Baker's yeast α-glucosidase enzyme. Compounds 1-17 exhibited a varying degree of α-glucosidase inhibitory activity with IC50 values between 35.83±0.66 and 297.99±1.20μM which are more better than the standard acarbose (IC50=774.5±1.94μM). Compound 10 and 14 showed significant inhibitory effects with IC50 value 50.57±0.81 and 35.83±0.66μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds.
    Matched MeSH terms: Molecular Docking Simulation
  15. 5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes
    Arshad T, Khan KM, Rasool N, Salar U, Hussain S, Asghar H, et al.
    Bioorg Chem, 2017 06;72:21-31.
    PMID: 28346872 DOI: 10.1016/j.bioorg.2017.03.007
    On the basis of previous report on promising α-glucosidase inhibitory activity of 5-bromo-2-aryl benzimidazole derivatives, these derivatives were further screened for urease inhibitory and cytotoxicity activity in order to get more potent and non-cytotoxic potential dual inhibitor for the patients suffering from diabetes as well as peptic ulcer. In this study, all compounds showed varying degree of potency in the range of (IC50=8.15±0.03-354.67±0.19μM) as compared to standard thiourea (IC50=21.25±0.15μM). It is worth mentioning that derivatives 7 (IC50=12.07±0.05μM), 8 (IC50=10.57±0.12μM), 11 (IC50=13.76±0.02μM), 14 (IC50=15.70±0.12μM) and 22 (IC50=8.15±0.03μM) were found to be more potent inhibitors than standard. All compounds were also evaluated for cytotoxicity towards 3T3 mouse fibroblast cell line and found to be completely non-toxic. Previously benzimidazole 1-25 were also showed α-glucosidase inhibitory potential. In silico studies were performed on the lead molecules i.e.2, 7, 8, 11, 14, and 22, in order to rationalize the binding interaction of compounds with the active site of urease enzyme.
    Matched MeSH terms: Molecular Docking Simulation
  16. Fulltext Characterization of α-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation
    Murugesu S, Ibrahim Z, Ahmed QU, Nik Yusoff NI, Uzir BF, Perumal V, et al.
    Molecules, 2018 Sep 19;23(9).
    PMID: 30235889 DOI: 10.3390/molecules23092402
    BACKGROUND: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity.

    METHODS: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS).

    RESULTS: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding.

    CONCLUSION: The study provides informative data on the potential α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.

    Matched MeSH terms: Molecular Docking Simulation
  17. New Hybrid Scaffolds based on Hydrazinyl Thiazole Substituted Coumarin; As Novel Leads of Dual Potential; In Vitro α-Amylase Inhibitory and Antioxidant (DPPH and ABTS Radical Scavenging) Activities
    Salar U, Khan KM, Chigurupati S, Syed S, Vijayabalan S, Wadood A, et al.
    Med Chem, 2019;15(1):87-101.
    PMID: 30179139 DOI: 10.2174/1573406414666180903162243
    BACKGROUND: Despite many side effects associated, there are many drugs which are being clinically used for the treatment of type-II diabetes mellitus (DM). In this scenario, there is still need to develop new therapeutic agents with more efficacy and less side effects. By keeping in mind the diverse spectrum of biological potential associated with coumarin and thiazole, a hybrid class based on these two heterocycles was synthesized.

    METHOD: Hydrazinyl thiazole substituted coumarins 4-20 were synthesized via two step reaction. First step was the acid catalyzed reaction of 3-formyl/acetyl coumarin derivatives with thiosemicarbazide to form thiosemicarbazone intermediates 1-3, followed by the reaction with different phenacyl bromides to afford products 4-20. All the synthetic analogs 4-20 were characterized by different spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR and 13C-NMR. Stereochemical assignment of the iminic double bond was carried out by the NOESY experiments. Elemental analysis was found in agreement with the calculated values.

    RESULTS: Compounds 4-20 were screened for α-amylase inhibitory activity and showed good activity in the range of IC50 = 1.829 ± 0.102-3.37 ± 0.17 µM as compared to standard acarbose (IC50 = 1.819 ± 0.19 µM). Compounds were also investigated for their DPPH and ABTS radical scavenging activities and displayed good radical scavenging potential. In addition to that molecular modelling study was conducted on all compounds to investigate the interaction details of compounds 4- 20 (ligands) with active site (receptor) of enzyme.

    CONCLUSION: The newly identified hybrid class may serve as potential lead candidates for the management of diabetes mellitus.

    Matched MeSH terms: Molecular Docking Simulation
  18. Discovery of natural product inhibitors of phosphodiesterase 10A as novel therapeutic drug for schizophrenia using a multistep virtual screening
    Al-Nema M, Gaurav A, Akowuah G
    Comput Biol Chem, 2018 Dec;77:52-63.
    PMID: 30240986 DOI: 10.1016/j.compbiolchem.2018.09.001
    The major complaint that most of the schizophrenic patients' face is the cognitive impairment which affects the patient's quality of life. The current antipsychotic drugs treat only the positive symptoms without alleviating the negative or cognitive symptoms of the disease. In addition, the existing therapies are known to produce extrapyramidal side effects that affect the patient adherence to the treatment. PDE10A inhibitor is the new therapeutic approach which has been proven to be effective in alleviating the negative and cognitive symptoms of the disease. A number of PDE10A inhibitors have been developed, but no inhibitor has made it beyond the clinical trials so far. Thus, the present study has been conducted to identify a PDE10A inhibitor from natural sources to be used as a lead compound for the designing of novel selective PDE10A inhibitors. Ligand and structure-based pharmacophore models for PDE10A inhibitors were generated and employed for virtual screening of universal natural products database. From the virtual screening results, 37 compounds were docked into the active site of the PDE10A. Out of 37 compounds, three inhibitors showed the highest affinity for PDE10A where UNPD216549 showed the lowest binding energy and has been chosen as starting point for designing of novel PDE10A inhibitors. The structure-activity-relationship studies assisted in designing of selective PDE10A inhibitors. The optimization of the substituents on the phenyl ring resulted in 26 derivatives with lower binding energy with PDE10A as compared to the lead compound. Among these, MA 8 and MA 98 exhibited the highest affinity for PDE10A with binding energy (-10.90 Kcal/mol).
    Matched MeSH terms: Molecular Docking Simulation
  19. Studies on the interaction of mononuclear metal(II) complexes of amino‑naphthoquinone with bio-macromolecules
    Kosiha A, Lo KM, Parthiban C, Elango KP
    Mater Sci Eng C Mater Biol Appl, 2019 Jan 01;94:778-787.
    PMID: 30423764 DOI: 10.1016/j.msec.2018.10.021
    Three metal(II) complexes [CoLCl2], [CuLCl2] and [ZnL2Cl2] {L = 2‑chloro‑3‑((3‑dimethylamino)propylamino)naphthalene‑1,4‑dione} have been synthesized and characterized using analytical, thermal and spectral techniques (FT-IR, UV-Vis, ESR and ESI-MS). The structure of the L has been confirmed by single crystal XRD study. The complexes show good binding propensity to bovine serum albumin (BSA) having relatively higher binding constant values (104 M-1) than the ligand. Fluorescence spectral studies indicate that [CoLCl2] binds relatively stronger with CT DNA through intercalative mode, exhibiting higher binding constant (2.22 × 105 M-1). Agarose gel electrophoresis run on plasmid DNA (pUC18) prove that all the complexes showed efficient DNA cleavage via hydroxyl radical mechanism. The complexes were identified as potent anticancer agents against two human cancer cell lines (MCF7 and A549) by comparing with cisplatin. Co(II) complex demonstrated greater cytotoxicity against MCF7 and A549 cells with IC50 values at 19 and 22 μM, respectively.
    Matched MeSH terms: Molecular Docking Simulation
  20. The development of a novel transforming growth factor-β (TGF-β) inhibitor that disrupts ligand-receptor interactions
    Wu H, Sun Y, Wong WL, Cui J, Li J, You X, et al.
    Eur J Med Chem, 2020 Mar 01;189:112042.
    PMID: 31958737 DOI: 10.1016/j.ejmech.2020.112042
    Transforming growth factor-β (TGF-β) plays an important role in regulating epithelial to mesenchymal transition (EMT) and the TGF-β signaling pathway is a potential target for therapeutic intervention in the development of many diseases, such as fibrosis and cancer. Most currently available inhibitors of TGF-β signaling function as TGF-β receptor I (TβR-I) kinase inhibitors, however, such kinase inhibitors often lack specificity. In the present study, we targeted the extracellular protein binding domain of the TGF-β receptor II (TβR-II) to interfere with the protein-protein interactions (PPIs) between TGF-β and its receptors. One compound, CJJ300, inhibited TGF-β signaling by disrupting the formation of the TGF-β-TβR-I-TβR-II signaling complex. Treatment of A549 cells with CJJ300 resulted in the inhibition of downstream signaling events such as the phosphorylation of key factors along the TGF-β pathway and the induction of EMT markers. Concomitant with these effects, CJJ300 significantly inhibited cell migration. The present study describes for the first time a designed molecule that can regulate TGF-β-induced signaling and EMT by interfering with the PPIs required for the formation of the TGF-β signaling complex. Therefore, CJJ300 can be an important lead compound with which to study TGF-β signaling and to design more potent TGF-β signaling antagonists.
    Matched MeSH terms: Molecular Docking Simulation
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