2. Academic Validation
  3. A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A

A matrix-focused structure-activity and binding site flexibility study of quinolinol inhibitors of botulinum neurotoxin serotype A

  • Bioorg Med Chem Lett. 2017 Feb 1;27(3):675-678. doi: 10.1016/j.bmcl.2016.11.019.
William A Harrell Jr 1,  Rebecca C Vieira 1,  Susan M Ensel 2,  Vicki Montgomery 1,  Rebecca Guernieri 1,  Vanessa S Eccard 1,  Yvette Campbell 1,  Virginia Roxas-Duncan 1,  John H Cardellina 2nd 1,  Robert P Webb 3,  Leonard A Smith 4
Affiliations

Affiliations

  • 1 Division of Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, United States.
  • 2 Department of Chemistry and Physics, Hood College, Frederick, MD 21701, United States.
  • 3 Division of Molecular and Translational Sciences, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, United States. Electronic address: robert.p.webb6.civ@mail.mil.
  • 4 Medical Countermeasures Technology, Office of the Chief Scientist, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, United States.
PMID: 28043798 DOI: 10.1016/j.bmcl.2016.11.019
Abstract

Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay.

Keywords

Betti reaction products; Binding site flexibility; BoNT/A inhibitor; Botulinum neurotoxin serotype A; Structure-activity relationship.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z