Biophysical Screening of a Focused Library for the Discovery of CYP121 Inhibitors as Novel Antimycobacterials.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Kamal, Ahmed A M
Cho, Sang Hyun
Franzblau, Scott G
Hartmann, Rolf W
MetadataShow full item record
AbstractThe 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.
AffiliationHIPS, Helmholtz-Institut für pharmazeutische Forschung Saarland, Universitätscampus 8.1, 66123 Saarbrücken, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 3.0 United States
- Development of ssDNA aptamers as potent inhibitors of Mycobacterium tuberculosis acetohydroxyacid synthase.
- Authors: Baig IA, Moon JY, Lee SC, Ryoo SW, Yoon MY
- Issue date: 2015 Oct
- Structure-based discovery of novel inhibitors of Mycobacterium tuberculosis CYP121 from Indonesian natural products.
- Authors: Prasasty VD, Cindana S, Ivan FX, Zahroh H, Sinaga E
- Issue date: 2020 Apr
- A Phenotypic Based Target Screening Approach Delivers New Antitubercular CTP Synthetase Inhibitors.
- Authors: Esposito M, Szadocka S, Degiacomi G, Orena BS, Mori G, Piano V, Boldrin F, Zemanová J, Huszár S, Barros D, Ekins S, Lelièvre J, Manganelli R, Mattevi A, Pasca MR, Riccardi G, Ballell L, Mikušová K, Chiarelli LR
- Issue date: 2017 Jun 9
- Discovery of Mycobacterium tuberculosis α-1,4-glucan branching enzyme (GlgB) inhibitors by structure- and ligand-based virtual screening.
- Authors: Dkhar HK, Gopalsamy A, Loharch S, Kaur A, Bhutani I, Saminathan K, Bhagyaraj E, Chandra V, Swaminathan K, Agrawal P, Parkesh R, Gupta P
- Issue date: 2015 Jan 2
- Screening of antitubercular compound library identifies novel ATP synthase inhibitors of Mycobacterium tuberculosis.
- Authors: Kumar S, Mehra R, Sharma S, Bokolia NP, Raina D, Nargotra A, Singh PP, Khan IA
- Issue date: 2018 Jan