165 research outputs found
Molecular insights into substrate binding mechanism of undecaprenyl pyrophosphate with membrane integrated phosphatidyl glycerophosphate phosphatase B (PgpB) using molecular dynamics simulation approach
No full textCe-SAD Phasing of Glucose Isomerase and Thermolysin Using Cu <i>Kα</i> Radiation
No full textMOLECULAR MODELLING, QSAR AND PHARMACOPHORE STUDIES ON ANTI-VIRAL, ANTI-MALARIAL AND ANTI-INFLAMMATORY BIOACTIVE COMPOUNDS FROM MARINE SOURCES
No full textMethyltransferase, human dihydrofolate reductase, and acidic mammalian chitinase are the potential targets for the viral, malarial and inflammatorydiseases, respectively. Hence, it is of interest to screen the natural compounds against these proteins using molecular docking. In this study,pharmacophore modeling was performed on marine compounds against these diseases using PHASE module. This resulted in the commonpharmacophore hypothesis AADRR.7f, which might be responsible for the biological activity: Two acceptor (A) groups (−C=O), one donor (O-H)and two aromatic rings (R). The three-dimensional-quantitative structure activity relationship model obtained has the correlation coefficient valuesq2=0.67; pred r2=0.86. In addition, molecular docking studies were performed. The model developed may serve as a query tool for future virtualscreening and drug designing for these targets. Marine compounds from the different marine sources such as alga, bacterium, sponges, soft corals, seacucumber, and clam have been selected from the literature.Keywords: Molecular modeling, Quantitative structure activity relationship, Pharmacophore, Methyltransferase, Human dihydrofolate reductase,Acidic mammalian chitinase, Absorption, distribution, metabolism and excretion, Docking, Structure based drug design
In-house SAD phasing with surface-bound cerium ions
No full textThe anomalous signal of cerium(III) ions present in a derivative of hen egg-white lysozyme (HEWL) crystals obtained by the addition of 0.025 M cerium chloride to the crystallization medium was used for phasing. X-ray intensity data were collected to 2 Å resolution using an in-house Cu Kα radiation data-collection facility. Phasing of a single-wavelength data set purely based on its f′′ led to a clearly interpretable electron-density map. Automated substructure solution by AutoSol in PHENIX resulted in four highest peaks corresponding to cerium(III) ions with data limited to 3 Å resolution, and about 90% of the residues were built automatically by AutoBuild in PHENIX. Cerium(III) ions bound on the surface of the enzyme are found to interact mainly with the main-chain and side-chain carbonyl groups of Asn, Glu, Tyr and Asp and with water molecules. Ce3+ ions were used as potential anomalous scatterers for the in-house single-wavelength anomalous scattering technique, and this is proposed as a tool for macromolecular phasing and for the study of the interactions of trivalent metal ions with proteins and other macromolecules.</jats:p
In vitro and in vivo anti-proliferative evaluation of bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex against Ehrlich ascites carcinoma tumors
No full textAbstract: The bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex [Cu(ttpy) ]Cl was synthesized and authenticated by single crystal analysis, which shows distorted octahedral geometry around copper(II) ion. The crystal packing is stabilized by C–H inter and intramolecular interactions. The complex was found to be lipophilic as determined by shake-flask method. In vitro cytotoxicity of the complex was tested against Ehrlich ascites carcinoma (EAC) and L6 myotube cell lines. The complex exhibit potent cytotoxicity with respect to the commercially available anticancer drug cisplatin. Hoechst 33258, AO/EB and PI (flow cytometry) staining methods suggest that the complex can induce apoptosis in EAC cells. Cell cycle analyses also support the induced apoptosis. Cellular uptake studies revealed that the complex can go into the cytoplasm and accumulate in the cell nuclei. The complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway by activating caspase 3 and caspase 7 and regulates the Bcl-2 family proteins. In vivo study of the complex was validated against the animal tumor growth (EAC) cell in Swiss albino mice. Graphical abstract: The bis(4′-(4-tolyl)-2,2′:6′,2″-terpyridine)copper(II) complex induces EAC cell apoptosis through a ROS-mediated mitochondrial pathway and significantly reduced the body weight and solid tumor volume in Swiss albino mice.No Full Tex
Targeting of DNA molecules, BSA/c-Met tyrosine kinase receptors and anti-proliferative activity of bis(terpyridine)copper(ii) complexes
No full textA series of homoleptic bis(terpyridine)copper(II) complexes of the type [Cu(L1–5)2]Cl2 (1–5), where L1–5 = 4′-(4-substituted)-2,2′:6′,2′′-terpyridines, have been synthesized and characterized. The molecular structure of complex 2 was confirmed by the single crystal XRD technique, and the geometry of the complexes is best described as distorted octahedral. Structural parameters from the crystallographic and DFT studies are in good agreement with each other. The small HOMO–LUMO energy gap supports bioefficacy of the complexes. DNA binding studies show high intrinsic binding constant values 1.53 ± 0.15, 1.62 ± 0.08 and 3.09 ± 0.12 × 105 M−1 for complexes 1, 2 and 3, respectively, with intercalative mode of binding to CT-DNA. The binding results were further supported by molecular docking studies. The experimental results indicate that the interaction between the complexes and BSA protein involves a static quenching mechanism. The molecular docking studies with c-Met tyrosine kinase receptors show hydrophobic and π–π interactions. All the complexes bring about hydroxyl radical mediated DNA cleavage in the presence of H2O2. In vitro cytotoxicities of the complexes (1–3) were tested against three cancerous cell lines, namely human breast adenocarcinoma (MCF-7), epithelioma (Hep-2) and cervical (HeLa) cell lines, and one non-tumorigenic human dermal fibroblast (NHDF) cell line by MTT reduction assay. The morphological assessment data obtained using Hoechst 33258 staining revealed that complex 3 induces apoptosis much more effectively than the other complexes.No Full Tex
Molecular insights into substrate binding mechanism of undecaprenyl pyrophosphate with membrane integrated phosphatidyl glycerophosphate phosphatase B (PgpB) using molecular dynamics simulation approach
No full textUndecaprenyl phosphate (C55-P) acts as carrier lipid in the synthesis of peptidoglycan, which is de novo synthesized from dephosphorylation of undecaprenyl pyrophosphate (C55-PP). The phosphatidylglycerol phosphate phosphatase B (PgpB) catalyzes the dephosphorylation of C55-PP and forms C55-P. As no structural study has been made regarding the binding of C55-PP to PgpB, in the current study, in silico molecular docking, followed by 150 ns molecular dynamics simulation of the putative binding complex in membrane/solvent environment has been performed to understand conformational dynamics. Results are compared with simulated apo form and PE inhibitor-bound form. Analysis of correlated residual fluctuation network in apo form, C55-PP bound and PE inhibitor-bound form suggests that difference in dynamic coupling between TM domain and α2 and α3 helix of periplasmic domain provides ligand binding to facilitate catalysis or to show inhibitory activity. Distance distribution in catalytic residual pair, H207-R104; H207-R201 and H207-D211 which stabilizes phosphate-enzyme intermediate shows a narrow peak in 2.4–3.6 Å in substrate-bound compared to apo form. Binding interactions and binding free energy analyses complement the partial inhibition of PE where PE has less binding free energy compared to the C55-PP substrate as well as the difference in binding interaction with catalytic pocket. Thus, the present study provides how substrate binding couples the movement in TM domain and periplasmic domain which might help in the understanding of active site communication in PgpB. C55-PP phosphatase interactions with a catalytic pocket of PgpB provide new insight for designing drugs against bacterial infection.</p
6b-Hydroxy-17-methyl-15-(3-nitrophenyl)-6b,7,16,17-tetrahydro-7,14a-methanonaphtho[1′,8′:1,2,3]pyrrolo[3′,2′:8,8a]azuleno[5,6-b]quinolin-14(15H)-one dichloromethane hemisolvate
No full textIn the title compound, C34H25N3O4·0.5CH2Cl2, which crystallized as a dichloromethane hemisolvate, the central 1-methylpyrrolidine ring adopts an envelope conformation with the N atom as the flap. The cyclopentane ring adopts a twist conformation on the CH—CH2 bond and the cyclohexane ring has an envelope conformation with the CH2 atom as the flap. The pyrrolidine ring mean plane makes dihedral angles of 40.09 (11), 69.21 (10) and 80.88 (8)° with the mean planes of the cyclopentane, cyclohexane and acenaphthylene rings, respectively. The 3-nitrobenzene ring is inclined to the acenaphthylene and quinoline ring systems by 69.32 (8) and 82.07 (7)°, respectively. There is an intramolecular O—H...N hydrogen bond present forming an S(5) ring motif. In the crystal, molecules are linked by C—H...O hydrogen bonds, forming sheets lying parallel to the ab plane, which enclose R22(18), R22(14), R22(12) and R22(16) ring motifs
Crystal structure of 15-(2-chlorophenyl)-6b-hydroxy-17-methyl-6b,7,16,17-tetrahydro-7,14a-methanonaphtho[1′,8′:1,2,3]pyrrolo[3′,2′:8,8a]azuleno[5,6-b]quinolin-14(15H)-one
No full textIn the title compound, C34H25ClN2O2, the fused pyrrolidine ring adopts an envelope conformation with the N atom as the flap. The two adjacent cyclopentane rings also adopt envelope conformations. The mean plane of the pyrrolidine ring makes dihedral angles of 40.53 (10) and 80.23 (10)° with the mean planes of the cyclopentane rings. The dihedral angle between the mean planes of the cyclopentane rings is 46.71 (9)°. An intramolecular O—H...N hydrogen bond is observed. In the crystal, molecules are linked by C—H...O, C—H...N and C—H...π interactions, forming a layer parallel to (10-2)
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