Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 228, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2021.113976
Keywords
FabG; ESKAPE Pathogens; Fatty acid biosynthesis; Broad spectrum
Categories
Funding
- Department of Biotechnology (DBT-Indo-Swedish project) , Govt. of India
- Vinnova [2017-00103]
- Swedish Research Council [2018-03999]
- Swedish Research Council [2018-03999] Funding Source: Swedish Research Council
- Vinnova [2018-03999] Funding Source: Vinnova
Ask authors/readers for more resources
This study focuses on the lead expansion of two hit molecules, resulting in the discovery of 43 analogues. Compounds 15 and 19 exhibit broad-spectrum inhibition activity against FabG.
Our previous studies on FabG have identified two compounds 5-bromo-2-(thiophene-2-carboxamido) benzoic acid (A) and ethyl 6-bromo-2-((dimethylamino)methyl)-5-hydroxy-1-phenyl-1H-indole-3carboxylate(B) as best hits with allosteric mode of inhibition. FabG is an integral part of bacterial fatty acid biosynthetic system FAS II shown to be an essential gene in most ESKAPE Pathogens. The current work is focussed on lead expansion of these two hit molecules which ended up with forty-three analogues (twenty-nine analogues from lead compound A and fourteen compounds from lead compound B). The enzyme inhibition studies revealed that compound 15 (effective against EcFabG, AbFabG, StFabG, MtFabG1) and 19 (inhibiting EcFabG and StFabG) had potency of broad-spectrum inhibition on FabG panel.(c) 2021 Published by Elsevier Masson SAS.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available