Aryl ureas represent a new class of anti-trypanosomal agents

Slides:

Advertisements

Similar presentations

COLORING WITH NUMBERS. NumbersNumbers NumbersNumbers

Advertisements

Structure-Based Computational Database Screening, In Vitro Assay, and NMR Assessment of Compounds that Target TAR RNA Kenneth E Lind, Zhihua Du, Koh Fujinaga,

Structure-Based Engineering of Angucyclinone 6-Ketoreductases

Volume 13, Issue 10, Pages (October 2006)

Structure of the Rho Transcription Terminator

Probing Structural Determinants Distal to the Site of Hydrolysis that Control Substrate Specificity of the 20S Proteasome Michael Groll, Tamim Nazif,

Simulations of HIV Capsid Protein Dimerization Reveal the Effect of Chemistry and Topography on the Mechanism of Hydrophobic Protein Association Naiyin.

Volume 10, Issue 5, Pages (November 2002)

Structural Basis for the Highly Selective Inhibition of MMP-13

Volume 21, Issue 4, Pages (April 2014)

Volume 21, Issue 3, Pages (March 2014)

Arvin C. Dar, Michael S. Lopez, Kevan M. Shokat Chemistry & Biology

Sebastian Meyer, Raimund Dutzler Structure

Volume 9, Issue 10, Pages (October 2002)

Volume 25, Issue 8, Pages e4 (August 2017)

Volume 19, Issue 10, Pages (October 2012)

Crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme: a new class of oxidative decarboxylases Yingwu Xu, Girija Bhargava, Hao Wu,

Mark Ultsch, Nathalie A Lokker, Paul J Godowski, Abraham M de Vos

Encapsulating Streptomycin within a Small 40-mer RNA

Volume 8, Issue 12, Pages (December 2001)

Volume 88, Issue 1, Pages (January 2005)

Combating Susceptibility to Drug Resistance

What Color is it?.

Jie Ji, Michael E Hogan, Xiaolian Gao Structure

Large-Scale Conformational Dynamics of the HIV-1 Integrase Core Domain and Its Catalytic Loop Mutants Matthew C. Lee, Jinxia Deng, James M. Briggs, Yong.

Simulations of HIV Capsid Protein Dimerization Reveal the Effect of Chemistry and Topography on the Mechanism of Hydrophobic Protein Association Naiyin.

Structure of a tRNA Repair Enzyme and Molecular Biology Workhorse

Volume 13, Issue 10, Pages (October 2006)

Volume 13, Issue 4, Pages (April 2006)

Catalytic Center Assembly of HPPK as Revealed by the Crystal Structure of a Ternary Complex at 1.25 Å Resolution Jaroslaw Blaszczyk, Genbin Shi, Honggao.

A biosynthetic thiolase in complex with a reaction intermediate: the crystal structure provides new insights into the catalytic mechanism Yorgo Modis,

Phospho-Pon Binding-Mediated Fine-Tuning of Plk1 Activity

Conversion of Squalene to the Pentacarbocyclic Hopene

The Process of Structure-Based Drug Design

Regulation of the Protein-Conducting Channel by a Bound Ribosome

Volume 15, Issue 9, Pages (September 2008)

Non-steroidal Anti-inflammatory Drugs Are Caspase Inhibitors

RIα Subunit of PKA Structure

Volume 12, Issue 11, Pages (November 2005)

Solution Structure of the RAIDD CARD and Model for CARD/CARD Interaction in Caspase-2 and Caspase-9 Recruitment James J Chou, Hiroshi Matsuo, Hanjun.

Volume 25, Issue 8, Pages e4 (August 2017)

Volume 6, Issue 3, Pages (March 1998)

Volume 8, Issue 6, Pages (June 2001)

Volume 5, Issue 2, Pages (February 1997)

Volume 12, Issue 7, Pages (July 2004)

Structural Basis for the Highly Selective Inhibition of MMP-13

The basis for K-Ras4B binding specificity to protein farnesyl-transferase revealed by 2 Å resolution ternary complex structures Stephen B Long, Patrick.

Replica Exchange Molecular Dynamics Simulations Provide Insight into Substrate Recognition by Small Heat Shock Proteins Sunita Patel, Elizabeth Vierling,

Structure-Based Engineering of Angucyclinone 6-Ketoreductases

Volume 9, Issue 12, Pages (December 2001)

Volume 7, Issue 7, Pages (July 2000)

Brownian Dynamics Simulations of the Interaction of Chlamydomonas Cytochrome f with Plastocyanin and Cytochrome c6 Elizabeth L. Gross, Douglas C. Pearson

Crystal Structure of the Human Myeloid Cell Activating Receptor TREM-1

Volume 22, Issue 9, Pages (September 2015)

Gregory J. Miller, James H. Hurley Molecular Cell

Ramon Hurtado-Guerrero, Daan M.F. van Aalten Chemistry & Biology

Color Box Button - Gray Type : object Type : object Type : object

Arvin C. Dar, Michael S. Lopez, Kevan M. Shokat Chemistry & Biology

Volume 11, Issue 4, Pages (April 2004)

HtrA—A Renaissance Protein

Molecular Similarity Analysis Uncovers Heterogeneous Structure-Activity Relationships and Variable Activity Landscapes Lisa Peltason, Jürgen Bajorath

Helicase structures: a new twist on DNA unwinding

The Structure of JNK3 in Complex with Small Molecule Inhibitors

Volume 10, Issue 4, Pages (April 2003)

Luc Bousset, Hassan Belrhali, Joël Janin, Ronald Melki, Solange Morera

Molecular Recognition of Cargo by the COPII Complex

Structure-Based Engineering of Angucyclinone 6-Ketoreductases

Volume 8, Issue 5, Pages (May 2000)

Stanley J Watowich, John J Skehel, Don C Wiley Structure

Presentation transcript:

Aryl ureas represent a new class of anti-trypanosomal agents Xiaohui Du, Elizabeth Hansell, Juan C Engel, Conor R Caffrey, Fred E Cohen, James H McKerrow Chemistry & Biology Volume 7, Issue 9, Pages 733-742 (September 2000) DOI: 10.1016/S1074-5521(00)00018-1

Figure 1 Structures of compounds having IC50 values below 10 μM for cruzain and rhodesain from a computational screening of the ACD database by DOCK4.0.1. Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Figure 2 The molecular surface of cruzain with Z-YA-FMK bound calculated by GRASP. Red color indicates that the surface is electronegative and purple color indicates that the surface is electropositive. The subsites are labeled yellow in the figure. Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Figure 3 Stereoview of the calculated orientation of compound D13 in the active site of cruzain by DOCK. The color coding of the cruzain residues is consistent with that of Table 1. The residues are color-coded according to the subsite pocket they belong. S3 pocket residues: purple; S2 pocket residues: red; S1 pocket residues: green; S1′ pocket residues: blue. The yellow residues labeled black are not easily associated with one of the pockets. D13 is color-coded by atom types, C: gray; N: blue; O: red; F, Cl: purple. Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Figure 4 Structures of compounds having activity below 10 μM possessing benzamide, sulfonamide, and aroyl urea scaffolds at a second stage miniscreen by GenX. The molecular weights and calculated CLogP values of each compound are shown in the figure. Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Figure 5 Synthesis of one of the compounds possessing the aroyl thiourea scaffold, D217. Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Figure 6 The synthesis of the compounds possessing the aroyl thiourea and urea scaffolds can apply common building blocks. Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Chemistry & Biology 2000 7, 733-742DOI: (10 Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Chemistry & Biology 2000 7, 733-742DOI: (10 Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)

Chemistry & Biology 2000 7, 733-742DOI: (10 Chemistry & Biology 2000 7, 733-742DOI: (10.1016/S1074-5521(00)00018-1)