- Mechanism of action of 5-nitrothiophenes against mycobacterium tuberculosis
-
On using the streptomycin-starved 18b strain as a model for nonreplicating Mycobacterium tuberculosis, we identified a 5-nitrothiophene compound as highly active but not cytotoxic. Mutants resistant to 5-nitrothiophenes were found be cross-resistant to the nitroimidazole PA-824 and unable to produce the F420 cofactor. Furthermore, 5-nitrothiophenes were shown to be activated by the F420-dependent nitroreductase Ddn and to release nitric oxide, a mechanism of action identical to that described for nitroimidazoles. Copyright
- Hartkoorn, Ruben C.,Ryabova, Olga B.,Chiarelli, Laurent R.,Riccardi, GioVanna,Makarov, Vadim,Makarov, Stewart T.
-
-
Read Online
- Synthesis and biological evaluation of thiazole derivatives as novel USP7 inhibitors
-
Herpesvirus-associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with and stabilizes Mdm2, and represents one of the first examples that deubiquitinases oncogenic proteins. USP7 has been regarded as a potential drug target for cancer therapy. Inhibitors of USP7 have been recently shown to suppress tumor cell growth in vitro and in vivo. Based on leading USP7 inhibitors P5091 and P22077, we designed and synthesized a series of thiazole derivatives. The results of in vitro assays showed that the thiazole compounds exhibited low micromolar inhibition activity against both USP7 enzyme and cancer cell lines. The compounds induced cell death in a p53-dependent and p53-independent manner. Taken together, this study may provide thiazole compounds as a new class of USP7 inhibitors.
- Chen, Chao,Song, Jiemei,Wang, Jinzheng,Xu, Chang,Chen, Caiping,Gu, Wei,Sun, Hongbin,Wen, Xiaoan
-
supporting information
p. 845 - 849
(2017/02/18)
-
- Selective oxidations of activated alcohols in water at room temperature
-
Allylic and benzylic alcohols can be selectively oxidized to their corresponding aldehydes or ketones in water containing nanoreactors composed of the designer surfactant TPGS-750-M. The oxidation relies on catalytic amounts of CuBr, bpy, and TEMPO, with N-methyl-imidazole; air is the stoichiometric oxidant. the Partner Organisations 2014.
- Lipshutz,Hageman,Fennewald,Linstadt,Slack,Voigtritter
-
supporting information
p. 11378 - 11381
(2014/11/08)
-
- Selective dual inhibitors of the cancer-related deubiquitylating proteases USP7 and USP47
-
Inhibitors of the cancer-related cysteine isopeptidase human ubiquitin-specific proteases 7 (USP7) and 47 (USP47) are considered to have potential as cancer therapeutics, owing to their ability to stabilize the tumor suppressor p53 and to decrease DNA polymerase β(Polβ), both of which are potential anticancer effects. A new class of dual small molecule inhibitors of these enzymes has been discovered. Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines. Compound 1 has been shown to demonstrate modest activity in human xenograft multiple myeloma and B-cell leukemia in vivo models. This activity may be the result of dual inhibition of USP7 and USP47. To address issues regarding potency and developability, analogues of compound 1 have been synthesized and tested, leading to improvements in potency, solubility, and metabolic reactivity profile. Further optimization is expected to yield preclinical candidates and, ultimately, clinical candidates for the treatment of multiple myeloma, prostate cancer, and other cancers.
- Weinstock, Joseph,Wu, Jian,Cao, Ping,Kingsbury, William D.,McDermott, Jeffrey L.,Kodrasov, Matthew P.,McKelvey, Devin M.,Suresh Kumar, K. G.,Goldenberg, Seth J.,Mattern, Michael R.,Nicholson, Benjamin
-
supporting information
p. 789 - 792,4
(2020/09/15)
-
- ANTI-NEOPLASTIC COMPOUNDS, COMPOSITIONS AND METHODS
-
Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.
- -
-
Page/Page column 26
(2010/11/03)
-