37525-57-8Relevant academic research and scientific papers
Optimization of Benzothiazole and Thiazole Hydrazones as Inhibitors of Schistosome BCL-2
Nguyen, William,Lee, Erinna F.,Evangelista, Marco,Lee, Mihwa,Harris, Tiffany J.,Colman, Peter M.,Smith, Nicholas A.,Williams, Luke B.,Jarman, Kate E.,Lowes, Kym N.,Haeberli, Cécile,Keiser, Jennifer,Smith, Brian J.,Fairlie, W. Douglas,Sleebs, Brad E.
, p. 1143 - 1163 (2021/02/22)
Limited therapeutic options are available for the treatment of human schistosomiasis caused by the parasitic Schistosoma flatworm. The B cell lymphoma-2 (BCL-2)-regulated apoptotic cell death pathway in schistosomes was recently characterized and shown to share similarities with the intrinsic apoptosis pathway in humans. Here, we exploit structural differences in the human and schistosome BCL-2 (sBCL-2) pro-survival proteins toward a novel treatment strategy for schistosomiasis. The benzothiazole hydrazone scaffold previously employed to target human BCL-XL was repurposed as a starting point to target sBCL-2. We utilized X-ray structural data to inform optimization and then applied a scaffold-hop strategy to identify the 5-carboxamide thiazole hydrazone scaffold (43) with potent sBCL-2 activity (IC50 30 nM). Human BCL-XL potency (IC50 13 nM) was inadvertently preserved during the optimization process. The lead analogues from this study exhibit on-target activity in model fibroblast cell lines dependent on either sBCL-2 or human BCL-XL for survival. Further optimization of the thiazole hydrazone class is required to exhibit activity in schistosomes and enhance the potential of this strategy for treating schistosomiasis.
BENZOXAZOLES, BENZTHIAZOLES AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Page/Page column 84-85, (2010/04/03)
Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin- modulating compound in combination with another therapeutic agent.
3-thioheteroaryl cephalosporin compounds, compositions and methods of use
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, (2008/06/13)
Cephalosporin compounds of the formula I STR1 are disclosed. The compounds are useful against MRSA/MRCNS. Compositions and methods of use are also included.
3-thioheteroaryl 1-carba-1-dethiacephalosporin compounds, compositions and methods of use
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, (2008/06/13)
1-Carba-1-dethiacephalosporin compounds of the formula I STR1 are disclosed. The compounds are useful against MRSA/MRCNS. Compositions and methods of use are also included.
Carbapenem antibacterial compounds, compositions containing such compounds and methods of treatment
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, (2008/06/13)
Carbapenems of the formula: STR1 are disclosed as useful antibacterial agents. Pharmaceutical compositions and methods of use are also disclosed.
