15018-50-5Relevant articles and documents
Selective cell adhesion inhibitors: Barbituric acid based α4β7-MAdCAM inhibitors
Harriman, Geraldine C.,Brewer, Matthias,Bennett, Robert,Kuhn, Cyrille,Bazin, Marc,Larosa, Greg,Skerker, Paul,Cochran, Nancy,Gallant, Debra,Baxter, Deborah,Picarella, Dominic,Jaffee, Bruce,Luly, Jay R.,Briskin, Michael J.
, p. 2509 - 2512 (2008)
A novel series of barbituric acid derivatives were identified as selective inhibitors of α4β7 MAdCAM (mucosal addressin cell adhesion molecule-1) interactions via a high throughput screening exercise. These inhibitors were optimized to submicromolar potencies in whole cell adhesion assays, retaining their selectivity over α4β1 VCAM.
Synthesis of N-aryl and N-arylcarbamoylamino derivatives of 1,3-diazinane-5-carboxamide and their activity against glioblastoma LN-229 cell line
Hron, Rebecca J.,Jursic, Branko S.,Neumann, Donna M.
, p. 6183 - 6193 (2016/12/06)
Six structural motifs based on the initial (lead) structure of merbarone were designed, prepared, and tested against the glioblastoma LN-229 cell line. Three different structural moieties were modified in the search for optimal glioblastoma activity: the 1,3-diazinane moiety, the aryl moiety, and the heteroatom linker. Calculated molecular descriptors such as lipophilicity (C log P), acidic strength (calculated pKa), and polar surface area (PSA) were used to design a diverse structural library of these compounds. From six different structural motifs and 136 compounds, a handful of examples with moderate (100 μg/ml), good (10 μg/ml) and excellent (1 μg/ml) glioblastoma activity were elucidated.
Synthesis and antifungal activity of substituted 2,4,6-pyrimidinetrione carbaldehyde hydrazones
Neumann, Donna M.,Cammarata, Amy,Backes, Gregory,Palmer, Glen E.,Jursic, Branko S.
, p. 813 - 826 (2014/01/23)
Opportunistic fungal infections caused by the Candida spp. are the most common human fungal infections, often resulting in severe systemic infections - a significant cause of morbidity and mortality in at-risk populations. Azole antifungals remain the mainstay of antifungal treatment for candidiasis, however development of clinical resistance to azoles by Candida spp. limits the drugs' efficacy and highlights the need for discovery of novel therapeutics. Recently, it has been reported that simple hydrazone derivatives have the capability to potentiate antifungal activities in vitro. Similarly, pyrimidinetrione analogs have long been explored by medicinal chemists as potential therapeutics, with more recent focus being on the potential for pyrimidinetrione antimicrobial activity. In this work, we present the synthesis of a class of novel hydrazone-pyrimidinetrione analogs using novel synthetic procedures. In addition, structure-activity relationship studies focusing on fungal growth inhibition were also performed against two clinically significant fungal pathogens. A number of derivatives, including phenylhydrazones of 5-acylpyrimidinetrione exhibited potent growth inhibition at or below 10 μM with minimal mammalian cell toxicity. In addition, in vitro studies aimed at defining the mechanism of action of the most active analogs provide preliminary evidence that these compound decrease energy production and fungal cell respiration, making this class of analogs promising novel therapies, as they target pathways not targeted by currently available antifungals.
