@article{milton_allen_feldmann_bobay_jung_stephens_melander_theisen_zeng_thompson_et al._2017, title={Structure of the Francisella response regulator QseB receiver domain, and characterization of QseB inhibition by antibiofilm 2-aminoimidazole-based compounds}, volume={106}, ISSN={["1365-2958"]}, DOI={10.1111/mmi.13759}, abstractNote={SummaryWith antibiotic resistance increasing at alarming rates, targets for new antimicrobial therapies must be identified. A particularly promising target is the bacterial two‐component system. Two‐component systems allow bacteria to detect, evaluate and protect themselves against changes in the environment, such as exposure to antibiotics and also to trigger production of virulence factors. Drugs that target the response regulator portion of two‐component systems represent a potent new approach so far unexploited. Here, we focus efforts on the highly virulent bacterium Francisella tularensis tularensis. Francisella contains only three response regulators, making it an ideal system to study. In this study, we initially present the structure of the N‐terminal domain of QseB, the response regulator responsible for biofilm formation. Subsequently, using binding assays, computational docking and cellular studies, we show that QseB interacts with2‐aminoimidazole based compounds that impede its function. This information will assist in tailoring compounds to act as adjuvants that will enhance the effect of antibiotics.}, number={2}, journal={MOLECULAR MICROBIOLOGY}, author={Milton, Morgan E. and Allen, C. Leigh and Feldmann, Erik A. and Bobay, Benjamin G. and Jung, David K. and Stephens, Matthew D. and Melander, Roberta J. and Theisen, Kelly E. and Zeng, Daina and Thompson, Richele J. and et al.}, year={2017}, month={Oct}, pages={223–235} } @article{stephens_yodsanit_melander_2016, title={Evaluation of ethyl N-(2-phenethyl) carbamate analogues as biofilm inhibitors of methicillin resistant Staphylococcus aureus}, volume={14}, ISSN={["1477-0539"]}, DOI={10.1039/c6ob00706f}, abstractNote={A small molecule library consisting of 45 compounds was synthesized based on the bacterial metabolite ethylN-(2-phenethyl) carbamate. From this library, a more potent, broad-spectrum inhibitor of MRSA biofilm formation was discovered.}, number={28}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Stephens, Matthew D. and Yodsanit, Nisakorn and Melander, Christian}, year={2016}, pages={6853–6856} } @article{melander_liu_stephens_bewley_melander_2016, title={Marine sponge alkaloids as a source of anti-bacterial adjuvants}, volume={26}, ISSN={["1464-3405"]}, DOI={10.1016/j.bmcl.2016.11.018}, abstractNote={Novel approaches that do not rely upon developing microbicidal compounds are sorely needed to combat multidrug resistant (MDR) bacteria. The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofilm formation and suppress antibiotic resistance.}, number={24}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Melander, Roberta J. and Liu, Hong-bing and Stephens, Matthew D. and Bewley, Carole A. and Melander, Christian}, year={2016}, month={Dec}, pages={5863–5866} } @article{stephens_yodsanit_melander_2016, title={Potentiation of the fosmidomycin analogue FR 900098 with substituted 2-oxazolines against Francisella novicida}, volume={7}, ISSN={["2040-2511"]}, DOI={10.1039/c6md00365f}, abstractNote={A library of 33 compounds was screened for potentiation of the antibiotic FR 900098 against the Francisella tularensis surrogate Francisella novicida.}, number={10}, journal={MEDCHEMCOMM}, author={Stephens, Matthew D. and Yodsanit, Nisakorn and Melander, Christian}, year={2016}, pages={1952–1956} } @article{naro_thomas_stephens_connelly_deiters_2015, title={Aryl amide small-molecule inhibitors of microRNA miR-21 function}, volume={25}, ISSN={["1464-3405"]}, DOI={10.1016/j.bmcl.2015.07.016}, abstractNote={MicroRNAs (miRNAs) are single stranded RNA molecules of ∼22 nucleotides that negatively regulate gene expression. MiRNAs are involved in fundamental cellular processes, such as development, differentiation, proliferation, and survival. MiRNA misregulation has been linked to various human diseases, most notably cancer. MicroRNA-21 (miR-21), a well-established oncomiR, is significantly overexpressed in many types of human cancers, thus rendering miR-21 a potential therapeutic target. Using a luciferase-based reporter assay under the control of miR-21 expression, a high-throughput screen of >300,000 compounds led to the discovery of a new aryl amide class of small-molecule miR-21 inhibitors. Structure–activity relationship (SAR) studies resulted in the development of four aryl amide derivatives as potent and selective miR-21 inhibitors. The intracellular levels of various miRNAs in HeLa cells were analyzed by qRT-PCR revealing specificity for miR-21 inhibition over other miRNAs. Additionally, preliminary mechanism of action studies propose a different mode of action compared to previously reported miR-21 inhibitors, thus affording a new chemical probe for future studies.}, number={21}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Naro, Yuta and Thomas, Meryl and Stephens, Matthew D. and Connelly, Colleen M. and Deiters, Alexander}, year={2015}, month={Nov}, pages={4793–4796} } @article{stephens_hubble_ernst_hoek_melander_cavanagh_melander_2016, title={Potentiation of Francisella resistance to conventional antibiotics through small molecule adjuvants}, volume={7}, ISSN={["2040-2511"]}, DOI={10.1039/c5md00353a}, abstractNote={A screen of 20 compounds identified small molecule adjuvants capable of potentiating antibiotic activity against Francisella philomiragia.}, number={1}, journal={MEDCHEMCOMM}, author={Stephens, Matthew D. and Hubble, Veroncia B. and Ernst, Robert K. and Hoek, Monique L. and Melander, Roberta J. and Cavanagh, John and Melander, Christian}, year={2016}, pages={128–131} }