Loading...
Biophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials.
Brengel, Christian Thomann, Andreas Schifrin, Alexander Allegretta, Giuseppe Kamal, Ahmed A M Haupenthal, Jörg Schnorr, Isabell Cho, Sang Hyun Franzblau, Scott G Empting, Martin
Brengel, Christian
Thomann, Andreas
Schifrin, Alexander
Allegretta, Giuseppe
Kamal, Ahmed A M
Haupenthal, Jörg
Schnorr, Isabell
Cho, Sang Hyun
Franzblau, Scott G
Empting, Martin
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2017-10-09
Submitted date
Files
Loading...
accepted manuscript
Adobe PDF, 941.84 KB
Loading...
supporting information
Adobe PDF, 1.54 MB
Other Titles
Abstract
The development of novel antimycobacterial agents against Mycobacterium tuberculosis (Mtb) is urgently required due to the appearance of multidrug resistance (MDR) combined with complicated long-term treatment. CYP121 was shown to be a promising novel target for inhibition of mycobacterial growth. In this study, we describe the rational discovery of new CYP121 inhibitors by a systematic screening based on biophysical and microbiological methods. The best hits originating from only one structural class gave initial information about molecular motifs required for binding and activity. The initial screening procedure was followed by mode-of-action studies and further biological characterizations. The results demonstrate superior antimycobacterial efficacy and a decreased toxicity profile of our frontrunner compound relative to the reference compound econazole. Due to its low molecular weight, promising biological profile, and physicochemical properties, this compound is an excellent starting point for further rational optimization.
Citation
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
Description
Series/Report no.
ISSN
1860-7187
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 3.0 United States