Literature DB >> 20155918

Synthesis and biological evaluation of botulinum neurotoxin a protease inhibitors.

Bing Li1, Ramdas Pai, Steven C Cardinale, Michelle M Butler, Norton P Peet, Donald T Moir, Sina Bavari, Terry L Bowlin.   

Abstract

NSC 240898 was previously identified as a botulinum neurotoxin A light chain (BoNT/A LC) endopeptidase inhibitor by screening the National Cancer Institute Open Repository diversity set. Two types of analogues have been synthesized and shown to inhibit BoNT/A LC in a FRET-based enzyme assay, with confirmation in an HPLC-based assay. These two series of compounds have also been evaluated for inhibition of anthrax lethal factor (LF), an unrelated metalloprotease, to examine enzyme specificity of the BoNT/A LC inhibition. The most potent inhibitor against BoNT/A LC in these two series is compound 12 (IC(50) = 2.5 microM, FRET assay), which is 4.4-fold more potent than the lead structure and 11.2-fold more selective for BoNT/A LC versus the anthrax LF metalloproteinase. Structure-activity relationship studies have revealed structural features important to potency and enzyme specificity.

Entities:  

Mesh:

Substances:

Year:  2010        PMID: 20155918      PMCID: PMC2841792          DOI: 10.1021/jm901852f

Source DB:  PubMed          Journal:  J Med Chem        ISSN: 0022-2623            Impact factor:   7.446


  30 in total

Review 1.  Identification of the major steps in botulinum toxin action.

Authors:  Lance L Simpson
Journal:  Annu Rev Pharmacol Toxicol       Date:  2004       Impact factor: 13.820

2.  A high-affinity competitive inhibitor of type A botulinum neurotoxin protease activity.

Authors:  James J Schmidt; Robert G Stafford
Journal:  FEBS Lett       Date:  2002-12-18       Impact factor: 4.124

Review 3.  Botulinum toxin as a biological weapon: medical and public health management.

Authors:  S S Arnon; R Schechter; T V Inglesby; D A Henderson; J G Bartlett; M S Ascher; E Eitzen; A D Fine; J Hauer; M Layton; S Lillibridge; M T Osterholm; T O'Toole; G Parker; T M Perl; P K Russell; D L Swerdlow; K Tonat
Journal:  JAMA       Date:  2001-02-28       Impact factor: 56.272

4.  Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons.

Authors:  Patrick G Foran; Nadiem Mohammed; Godfrey O Lisk; Sharuna Nagwaney; Gary W Lawrence; Eric Johnson; Leonard Smith; K Roger Aoki; J Oliver Dolly
Journal:  J Biol Chem       Date:  2002-10-14       Impact factor: 5.157

5.  Potent neutralization of botulinum neurotoxin by recombinant oligoclonal antibody.

Authors:  A Nowakowski; C Wang; D B Powers; P Amersdorfer; T J Smith; V A Montgomery; R Sheridan; R Blake; L A Smith; J D Marks
Journal:  Proc Natl Acad Sci U S A       Date:  2002-08-12       Impact factor: 11.205

6.  Fluorigenic substrates for the protease activities of botulinum neurotoxins, serotypes A, B, and F.

Authors:  James J Schmidt; Robert G Stafford
Journal:  Appl Environ Microbiol       Date:  2003-01       Impact factor: 4.792

7.  Identification of small molecule inhibitors of anthrax lethal factor.

Authors:  Rekha G Panchal; Ann R Hermone; Tam Luong Nguyen; Thiang Yian Wong; Robert Schwarzenbacher; James Schmidt; Douglas Lane; Connor McGrath; Benjamin E Turk; James Burnett; M Javad Aman; Stephen Little; Edward A Sausville; Daniel W Zaharevitz; Lewis C Cantley; Robert C Liddington; Rick Gussio; Sina Bavari
Journal:  Nat Struct Mol Biol       Date:  2003-12-29       Impact factor: 15.369

Review 8.  Botulin toxin: a weapon in terrorism.

Authors:  Deborah Josko
Journal:  Clin Lab Sci       Date:  2004

9.  Benzylidene cyclopentenediones: First irreversible inhibitors against botulinum neurotoxin A's zinc endopeptidase.

Authors:  Katerina Capková; Mark S Hixon; Sabine Pellett; Joseph T Barbieri; Eric A Johnson; Kim D Janda
Journal:  Bioorg Med Chem Lett       Date:  2009-10-31       Impact factor: 2.823

Review 10.  Therapy and prophylaxis of inhaled biological toxins.

Authors:  Brian M Paddle
Journal:  J Appl Toxicol       Date:  2003 May-Jun       Impact factor: 3.446

View more
  12 in total

1.  Selective syntheses of no-carrier-added 2- and 3-[18F]fluorohalopyridines through the radiofluorination of halopyridinyl(4'-methoxyphenyl)iodonium tosylates.

Authors:  Joong-Hyun Chun; Victor W Pike
Journal:  Chem Commun (Camb)       Date:  2012-08-30       Impact factor: 6.222

2.  Synthesis and antibacterial evaluation of new, unsymmetrical triaryl bisamidine compounds.

Authors:  Son T Nguyen; John D Williams; Michelle M Butler; Xiaoyuan Ding; Debra M Mills; Tommy F Tashjian; Rekha G Panchal; Susan K Weir; Chaeho Moon; Hwa-Ok Kim; Jeremiah A Marsden; Norton P Peet; Terry L Bowlin
Journal:  Bioorg Med Chem Lett       Date:  2014-06-12       Impact factor: 2.823

3.  Activity of diimidazoline amides against African trypanosomiasis.

Authors:  Yuxiang Dong; Xiaofang Wang; Monica Cal; Marcel Kaiser; Jonathan L Vennerstrom
Journal:  Bioorg Med Chem Lett       Date:  2013-12-22       Impact factor: 2.823

4.  Time-dependent botulinum neurotoxin serotype A metalloprotease inhibitors.

Authors:  Bing Li; Steven C Cardinale; Michelle M Butler; Ramdas Pai; Jonathan E Nuss; Norton P Peet; Sina Bavari; Terry L Bowlin
Journal:  Bioorg Med Chem       Date:  2011-10-26       Impact factor: 3.641

5.  The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease.

Authors:  Igor Opsenica; Vuk Filipovic; Jon E Nuss; Laura M Gomba; Dejan Opsenica; James C Burnett; Rick Gussio; Bogdan A Solaja; Sina Bavari
Journal:  Eur J Med Chem       Date:  2012-03-30       Impact factor: 6.514

6.  Development of a comprehensive, validated pharmacophore hypothesis for anthrax toxin lethal factor (LF) inhibitors using genetic algorithms, Pareto scoring, and structural biology.

Authors:  Ting-Lan Chiu; Elizabeth A Amin
Journal:  J Chem Inf Model       Date:  2012-06-25       Impact factor: 4.956

7.  Highly predictive support vector machine (SVM) models for anthrax toxin lethal factor (LF) inhibitors.

Authors:  Xia Zhang; Elizabeth Ambrose Amin
Journal:  J Mol Graph Model       Date:  2015-11-17       Impact factor: 2.518

8.  Potent and broad-spectrum antibacterial activity of indole-based bisamidine antibiotics: synthesis and SAR of novel analogs of MBX 1066 and MBX 1090.

Authors:  John D Williams; Son T Nguyen; Shen Gu; Xiaoyuan Ding; Michelle M Butler; Tommy F Tashjian; Timothy J Opperman; Rekha G Panchal; Sina Bavari; Norton P Peet; Donald T Moir; Terry L Bowlin
Journal:  Bioorg Med Chem       Date:  2013-10-25       Impact factor: 3.641

9.  Structural framework for covalent inhibition of Clostridium botulinum neurotoxin A by targeting Cys165.

Authors:  Enrico A Stura; Laura Le Roux; Karine Guitot; Sandra Garcia; Sarah Bregant; Fabrice Beau; Laura Vera; Guillaume Collet; Denis Ptchelkine; Huseyin Bakirci; Vincent Dive
Journal:  J Biol Chem       Date:  2012-08-06       Impact factor: 5.157

10.  Small-molecule quinolinol inhibitor identified provides protection against BoNT/A in mice.

Authors:  Padma Singh; Manglesh Kumar Singh; Dilip Chaudhary; Vinita Chauhan; Pranay Bharadwaj; Apurva Pandey; Nisha Upadhyay; Ram Kumar Dhaked
Journal:  PLoS One       Date:  2012-10-11       Impact factor: 3.240

View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.