scholarly journals Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin--new carriers of alkylating elements.

2000 ◽  
Vol 47 (1) ◽  
pp. 23-35 ◽  
Author(s):  
D Bartulewic ◽  
A Markowska ◽  
S Wołczyński ◽  
M Dabrowska ◽  
A Rózański
Keyword(s):  
Molecular Modelling ◽  
Methoxy Group ◽  
Antitumour Activity ◽  
National Laboratory ◽  
Data Bank ◽  
Brookhaven National Laboratory ◽  
Ortho Position ◽  
Standard Cell ◽  
New Compounds ◽  
Mcf 7

A series of netropsin and distamycin analogues was synthesised and investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7.

scholarly journals Protein Data Bank (PDB): Database of Three-Dimensional Structural Information of Biological Macromolecules

1998 ◽  
Vol 54 (6) ◽  
pp. 1078-1084 ◽  
Author(s):  
Joel L. Sussman ◽  
Dawei Lin ◽  
Jiansheng Jiang ◽  
Nancy O. Manning ◽  
Jaime Prilusky ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Protein Data Bank ◽  
Structural Information ◽  
National Laboratory ◽  
Three Dimensional ◽  
Data Bank ◽  
Brookhaven National Laboratory ◽  
Biological Macromolecules

The Protein Data Bank (PDB) at Brookhaven National Laboratory, is a database containing experimentally determined three-dimensional structures of proteins, nucleic acids and other biological macromolecules, with approximately 8000 entries. Data are easily submittedviaPDB's WWW-based toolAutoDep, in either mmCIF or PDB format, and are most conveniently examinedviaPDB's WWW-based tool3DB Browser.

scholarly journals Docking studies, synthesis, characterization, and cytotoxicity activity of new bis-chalcones derivatives

2021 ◽  
Vol 8 (4) ◽  
pp. 4294-4305
Author(s):  
Mohammad Murwih Alidmat ◽  
Melati Khairuddean ◽  
Salizawati Muhamad Salhimi ◽  
Mohammad Al-Amin
Keyword(s):  
Inhibitory Concentration ◽  
Data Bank ◽  
2D Nmr ◽  
Docking Studies ◽  
Standard Drug ◽  
Discovery Studio ◽  
Cytotoxicity Activity ◽  
Diphenyl Tetrazolium Bromide ◽  
New Compounds ◽  
Mcf 7

Introduction: A bis-chalcones were prepared by the reaction of terephthalaldehyde with 3-acetyl-2,5-dichlorothiophene or 3-acetyl- 5-chlorothiophene and reaction cyclo ketone derivatives with phenyl aldehyde derivatives in good yields. Methods: The molecular docking studies were conducted using the Discovery Studio (DSv4.5) and MG. Tools installed in Window 10. The cancer receptor (3ERT) was downloaded from the protein data bank (PDB). All new compounds were characterized by IR, 1H-NMR, 13C-NMR, 2D-NMR, and CHN elemental analysis. The anticancer activity of the synthesized compounds was determined using MTT (3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) reduction assay against MCF-7 cells, and then the minimum inhibitory concentration (IC50) was determined with the reference of the standard drug tamoxifen. Results: The results showed that compound 6 showed more potent activity in inhibiting growth on both types of MCF-7 compared to reference tamoxifen.    

A New Cytotoxic Brominated Acetylenic Hydrocarbon from the Marine Sponge Haliclona sp. with a Selective Effect against Human Breast Cancer

2013 ◽  
Vol 68 (1-2) ◽  
pp. 70-75 ◽  
Author(s):  
Walied M. Alarif ◽  
Ahmed Abdel-Lateff ◽  
Sultan S. Al-Lihaibi ◽  
Seif-Eldin N. Ayyad ◽  
Farid A. Badria
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Antitumour Activity ◽  
Human Breast ◽  
African Green Monkey Kidney ◽  
Acetylenic Hydrocarbon ◽  
New Compounds ◽  
First Time ◽  
Natural Metabolite ◽  
Mcf 7

3 Three acetylenic brominated derivatives were isolated from a Red Sea sponge, Haliclona sp. One of them, 18-bromooctadeca-9(E),17(E)-dien-7,15-diynoic acid (), is a known metabolite, and the other two are new compounds, (1E,5E,12E,19E)-1,22-dibromodocosa- 1,5,12,19-tetraen-3,14,21-triyne (1) and methyl 18-bromooctadeca-9(E),17(E)-dien-7,15- diynoate (2) which was isolated for the first time as a natural metabolite. Structures of all compounds were determined based on extensive spectroscopic measurements [1D (1H, 13C and DEPT) and 2D (HSQC, HMBC and NOESY) NMR, MS, UV, and IR]. All compounds, except 3, were evaluated for their cytotoxicity employing four cancer cell lines, i.e. MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), WI-38 (skin carcinoma), and Vero (African green monkey kidney). Compounds 1 and 2 had potent selective antitumour activity towards MCF-7 cells with IC50 values of 32.5 and 50.8 μM, respectively

De la Mioglobina al SARS-CoV-2: ¡50 años del Protein Data Bank!

2022 ◽  
Vol 33 (1) ◽  
pp. 50
Author(s):  
Eduardo Sánchez-Lara
Keyword(s):  
Protein Data Bank ◽  
National Laboratory ◽  
Data Bank ◽  
Brookhaven National Laboratory ◽  
Acceso Abierto

<p><span>La Mioglobina fue la primer proteína visualizada en tres dimensiones (3D) a través de la cristalografía de rayos-X, sentando las bases para una nueva era de comprensión biológica. A partir de este hecho, se comenzaron a determinar estructuralmente una serie de macromoléculas de considerable interés biológico. Sin embargo, este impresionante avance en las ciencias de la vida, contrastaba radicalmente con la ausencia de un repositorio global para archivar y compartir los datos cristalográficos colectados de los experimentos de difracción. Con el propósito de llenar este vacío, en 1971 se estableció el Protein Data Bank (PDB) en el Brookhaven National Laboratory, como el único almacén central de estructuras 3D de macromoléculas biológicas. Establecido con apenas siete estructuras, el PDB ha evolucionado a un gigantesco repositorio de acceso abierto, almacenando datos estructurales de más de 170,000 biomoléculas, principalmente de proteínas y ácidos nucleicos. Además de ser un banco de datos biológicos, el PDB sirve como un portal educativo a través del PDB-101, ofreciendo un conjunto de recursos extraordinarios para admirar el mundo biológico. En esta revisión, festejamos los 50 años de oro del PDB con una mirada a su historia y un recorrido por algunas herramientas educativas que el archivo pone a disposición de estudiantes, investigadores, profesores y público no especializado. Ilustramos el valor de estos recursos con la estructura 3D de la maquinaria biológica recientemente depositada en el archivo, del ubicuo y nuevo coronavirus causante del síndrome respiratorio agudo severo (SARS-CoV-2) o COVID-19.</span></p>

Chemical and orientational imaging of polymeric samples

1994 ◽  
Vol 52 ◽  
pp. 68-69
Author(s):  
H. Ade ◽  
B. Hsiao ◽  
G. Mitchell ◽  
E. Rightor ◽  
A. P. Smith ◽  
...  
Keyword(s):  
Ethylene Terephthalate ◽  
National Laboratory ◽  
Brookhaven National Laboratory ◽  
Carbonyl Groups ◽  
Aromatic Rings ◽  
Edge Structure ◽  
X Ray ◽  
Scanning Transmission ◽  
Polymeric Samples ◽  
X Ray Absorption

We have used the Scanning Transmission X-ray Microscope at beamline X1A (X1-STXM) at Brookhaven National Laboratory (BNL) to acquire high resolution, chemical and orientation sensitive images of polymeric samples as well as point spectra from 0.1 μm areas. This sensitivity is achieved by exploiting the X-ray Absorption Near Edge Structure (XANES) of the carbon K edge. One of the most illustrative example of the chemical sensitivity achievable is provided by images of a polycarbonate/pol(ethylene terephthalate) (70/30 PC/PET) blend. Contrast reversal at high overall contrast is observed between images acquired at 285.36 and 285.69 eV (Fig. 1). Contrast in these images is achieved by exploring subtle differences between resonances associated with the π bonds (sp hybridization) of the aromatic groups of each polymer. PET has a split peak associated with these aromatic groups, due to the proximity of its carbonyl groups to its aromatic rings, whereas PC has only a single peak.

Design, Synthesis and Antitumor Assessment of Phenylureas Bearing 5-Fluoroindolin-2-one Moiety

2020 ◽  
Vol 16 (7) ◽  
pp. 958-968
Author(s):  
Yunrui Cai ◽  
Tong Chen ◽  
Huajian Zhu ◽  
Hongbin Zou
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Human Cancer ◽  
The Body ◽  
Human Breast ◽  
Design Synthesis ◽  
Human Carcinoma ◽  
Xenograft Models ◽  
New Compounds ◽  
Mcf 7

Background: The development of novel antineoplastic agents remains highly desirable. Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas bearing 5-fluoroindolin-2-one moiety. Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative ability was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast cancer (MCF-7). Results: A total of twenty-one new compounds were synthesized and characterized by means of 1H and 13C NMR as well as HR-MS. Three sets of compounds (1a‒1c, 2a‒2c, and 3a‒3c) were initially constructed, and preliminary antiproliferative activities of these molecules were evaluated against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a‒1c) as the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d‒1o) were then designed and synthesized for structure-activity relationship study. Most of the new compounds showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cytotoxic effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM. Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF- 7) xenograft models without affecting the body weight of its recipients. Conclusion: In this study, twenty-one new compounds, containing the privileged structures of phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structureactivity studies showed that 1g was the most bioactive antitumor agent among all tested compounds, hence a potentially promising lead compound once given further optimization.

Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors

2020 ◽  
Vol 75 (9-10) ◽  
pp. 353-362
Author(s):  
Begüm Nurpelin Sağlık ◽  
Ahmet Mücahit Şen ◽  
Asaf Evrim Evren ◽  
Ulviye Acar Çevik ◽  
Derya Osmaniye ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Biological Effects ◽  
Docking Studies ◽  
Benzimidazole Derivatives ◽  
Binding Modes ◽  
Reference Drug ◽  
In Silico Studies ◽  
New Compounds ◽  
Mcf 7

AbstractInhibition of aromatase enzymes is very important in the prevention of estrogen-related diseases and the regulation of estrogen levels. Aromatase enzyme is involved in the final stage of the biosynthesis of estrogen, in the conversion of androgens to estrogen. The development of new compounds for the inhibition of aromatase enzymes is an important area for medicinal chemists in this respect. In the present study, new benzimidazole derivatives have been designed and synthesized which have reported anticancer activity in the literature. Their anticancer activity was evaluated against human A549 and MCF-7 cell lines by MTT assay. In the series, concerning MCF-7 cell line, the most potent compounds were the 4-benzylpiperidine derivatives 2c, 2g, and 2k with IC50 values of 0.032 ± 0.001, 0.024 ± 0.001, and 0.035 ± 0.001 µM, respectively, compared to the reference drug cisplatin (IC50 = 0.021 ± 0.001 µM). Then, these compounds were subject to further in silico aromatase enzyme inhibition assays to determine the possible binding modes and interactions underlying their activity. Thanks to molecular docking studies, the effectiveness of these compounds against aromatase enzyme could be simulated. Consequently, it has been found that these compounds can be settled very properly to the active site of the aromatase enzyme.

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