Literature DB >> 23453069

Design, synthesis, and biological activity of diaryl ether inhibitors of Toxoplasma gondii enoyl reductase.

Gang Cheng1, Stephen P Muench, Ying Zhou, Gustavo A Afanador, Ernest J Mui, Alina Fomovska, Bo Shiun Lai, Sean T Prigge, Stuart Woods, Craig W Roberts, Mark R Hickman, Patty J Lee, Susan E Leed, Jennifer M Auschwitz, David W Rice, Rima McLeod.   

Abstract

Triclosan is a potent inhibitor of Toxoplasma gondii enoyl reductase (TgENR), which is an essential enzyme for parasite survival. In view of triclosan's poor druggability, which limits its therapeutic use, a new set of B-ring modified analogs were designed to optimize its physico-chemical properties. These derivatives were synthesized and evaluated by in vitro assay and TgENR enzyme assay. Some analogs display improved solubility, permeability and a comparable MIC50 value to that of triclosan. Modeling of these inhibitors revealed the same overall binding mode with the enzyme as triclosan, but the B-ring modifications have additional interactions with the strongly conserved Asn130.
Copyright © 2013 Elsevier Ltd. All rights reserved.

Entities:  

Mesh：

Substances：

Year:  2013        PMID： 23453069      PMCID： PMC3625046          DOI： 10.1016/j.bmcl.2013.02.019

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  32 in total

1.  Severe congenital toxoplasmosis in the United States: clinical and serologic findings in untreated infants.

Authors:  Tudor Rares Olariu; Jack S Remington; Rima McLeod; Ambereen Alam; Jose G Montoya
Journal:  Pediatr Infect Dis J       Date:  2011-12       Impact factor: 2.129

Review 2.  Congenital toxoplasmosis. The Toxoplasmosis Study Group.

Authors:  C N Swisher; K Boyer; R McLeod
Journal:  Semin Pediatr Neurol       Date:  1994-09       Impact factor: 1.636

3.  Congenital toxoplasmosis. A prospective study of 378 pregnancies.

Authors:  G Desmonts; J Couvreur
Journal:  N Engl J Med       Date:  1974-05-16       Impact factor: 91.245

4.  Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 1: 4'-substituted triclosan derivatives.

Authors:  Joel S Freundlich; John W Anderson; Dimitri Sarantakis; Hong-Ming Shieh; Min Yu; Juan-Carlos Valderramos; Edinson Lucumi; Mack Kuo; William R Jacobs; David A Fidock; Guy A Schiehser; David P Jacobus; James C Sacchettini
Journal:  Bioorg Med Chem Lett       Date:  2005-09-29       Impact factor: 2.823

5.  Apicoplast fatty acid synthesis is essential for organelle biogenesis and parasite survival in Toxoplasma gondii.

Authors:  Jolly Mazumdar; Emma H Wilson; Kate Masek; Christopher A Hunter; Boris Striepen
Journal:  Proc Natl Acad Sci U S A       Date:  2006-08-18       Impact factor: 11.205

6.  Unrecognized ingestion of Toxoplasma gondii oocysts leads to congenital toxoplasmosis and causes epidemics in North America.

Authors:  Kenneth Boyer; Dolores Hill; Ernest Mui; Kristen Wroblewski; Theodore Karrison; J P Dubey; Mari Sautter; A Gwendolyn Noble; Shawn Withers; Charles Swisher; Peter Heydemann; Tiffany Hosten; Jane Babiarz; Daniel Lee; Paul Meier; Rima McLeod
Journal:  Clin Infect Dis       Date:  2011-10-21       Impact factor: 9.079

Review 7.  Toxoplasmic encephalitis in AIDS.

Authors:  B J Luft; J S Remington
Journal:  Clin Infect Dis       Date:  1992-08       Impact factor: 9.079

8.  Early and longitudinal evaluations of treated infants and children and untreated historical patients with congenital toxoplasmosis: the Chicago Collaborative Treatment Trial.

Authors:  J McAuley; K M Boyer; D Patel; M Mets; C Swisher; N Roizen; C Wolters; L Stein; M Stein; W Schey
Journal:  Clin Infect Dis       Date:  1994-01       Impact factor: 9.079

9.  Type I and type II fatty acid biosynthesis in Eimeria tenella: enoyl reductase activity and structure.

Authors:  J Z Lu; S P Muench; M Allary; S Campbell; C W Roberts; E Mui; R L McLeod; D W Rice; S T Prigge
Journal:  Parasitology       Date:  2007-08-13       Impact factor: 3.234

10.  Delivery of antimicrobials into parasites.

Authors:  B U Samuel; B Hearn; D Mack; P Wender; J Rothbard; M J Kirisits; E Mui; S Wernimont; C W Roberts; S P Muench; D W Rice; S T Prigge; A B Law; R McLeod
Journal:  Proc Natl Acad Sci U S A       Date:  2003-11-17       Impact factor: 11.205
View more
  7 in total

1.  The benzimidazole based drugs show good activity against T. gondii but poor activity against its proposed enoyl reductase enzyme target.

Authors:  Craig Wilkinson; Martin J McPhillie; Ying Zhou; Stuart Woods; Gustavo A Afanador; Shaun Rawson; Farzana Khaliq; Sean T Prigge; Craig W Roberts; David W Rice; Rima McLeod; Colin W Fishwick; Stephen P Muench
Journal:  Bioorg Med Chem Lett       Date:  2013-12-22       Impact factor: 2.823

2.  Discrimination of potent inhibitors of Toxoplasma gondii enoyl-acyl carrier protein reductase by a thermal shift assay.

Authors:  Gustavo A Afanador; Stephen P Muench; Martin McPhillie; Alina Fomovska; Arne Schön; Ying Zhou; Gang Cheng; Jozef Stec; Joel S Freundlich; Hong-Ming Shieh; John W Anderson; David P Jacobus; David A Fidock; Alan P Kozikowski; Colin W Fishwick; David W Rice; Ernesto Freire; Rima McLeod; Sean T Prigge
Journal:  Biochemistry       Date:  2013-12-13       Impact factor: 3.162

3.  Modification of triclosan scaffold in search of improved inhibitors for enoyl-acyl carrier protein (ACP) reductase in Toxoplasma gondii.

Authors:  Jozef Stec; Alina Fomovska; Gustavo A Afanador; Stephen P Muench; Ying Zhou; Bo-Shiun Lai; Kamal El Bissati; Mark R Hickman; Patty J Lee; Susan E Leed; Jennifer M Auschwitz; Caroline Sommervile; Stuart Woods; Craig W Roberts; David Rice; Sean T Prigge; Rima McLeod; Alan P Kozikowski
Journal:  ChemMedChem       Date:  2013-06-14       Impact factor: 3.466

4.  Triazole-based compound as a candidate to develop novel medicines to treat toxoplasmosis.

Authors:  Katarzyna Dzitko; Agata Paneth; Tomasz Plech; Jakub Pawełczyk; Lidia Węglińska; Piotr Paneth
Journal:  Antimicrob Agents Chemother       Date:  2014-10-06       Impact factor: 5.191

5.  Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides.

Authors:  Stephen P Muench; Jozef Stec; Ying Zhou; Gustavo A Afanador; Martin J McPhillie; Mark R Hickman; Patty J Lee; Susan E Leed; Jennifer M Auschwitz; Sean T Prigge; David W Rice; Rima McLeod
Journal:  Bioorg Med Chem Lett       Date:  2013-04-24       Impact factor: 2.823

Review 6.  Drugs in development for toxoplasmosis: advances, challenges, and current status.

Authors:  P Holland Alday; Joseph Stone Doggett
Journal:  Drug Des Devel Ther       Date:  2017-01-25       Impact factor: 4.162

7.  The application of "plug-in molecules" method in novel strobilurin fungicides screening.

Authors:  Xuelian Liu; Dongyan Yang; Fahong Yin; Jia-Qi Li; Yumei Xiao; Bin Fu; Zhaohai Qin
Journal:  RSC Adv       Date:  2020-11-24       Impact factor: 4.036
  7 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.