@article{stowe_thompson_peng_su_blackledge_draughn_coe_johannes_lapham_mackenzie_et al._2015, title={Membrane-Permeabilizing Activity of Reverse-Amide 2-Aminoimidazole Antibiofilm Agents Against Acinetobacter baumannii}, volume={12}, ISSN={["1875-5704"]}, DOI={10.2174/1567201811666140924125740}, abstractNote={Acinetobacter baumannii has quickly become one of the most insidious and prevalent nosocomial infections. Recently, the reverse-amide class of 2-aminoimidazole compounds (RA-2AI) was found both to prevent A. baumannii biofilm formation and also to disperse preexisting formations, putatively through interactions with cytosolic response regulators. Here we focus on how this class of antibiofilm agent traverses cellular membranes. Following the discovery of dosage-dependent growth rate changes, the cellular effects of RA-2AI were investigated using a combination of molecular assays and microscopic techniques. It was found that RA-2AI exposure has measureable effects on the bacterial membranes, resulting in a period of increased permeability and visible structural aberrations. Based on these results, we propose a model that describes how the structure of RA-2AI allows it to insert itself into and disrupt the fluidity of the membrane, creating an opportunity for increased molecular permeability.}, number={2}, journal={CURRENT DRUG DELIVERY}, author={Stowe, Sean D. and Thompson, Richele J. and Peng, Lingling and Su, Zhaoming and Blackledge, Meghan S. and Draughn, G. Logan and Coe, William H. and Johannes, Eva and Lapham, Valerie K. and Mackenzie, John and et al.}, year={2015}, pages={223–230} }
 @article{thompson_bobay_stowe_olson_peng_su_actis_melander_cavanagh_2012, title={Identification of BfmR, a Response Regulator Involved in Biofilm Development, as a Target for a 2-Aminoimidazole-Based Antibiofilm Agent}, volume={51}, ISSN={["0006-2960"]}, DOI={10.1021/bi3015289}, abstractNote={2-Aminoimidazoles (2AIs) have been documented to disrupt bacterial protection mechanisms, including biofilm formation and genetically encoded antibiotic resistance traits. Using Acinetobacter baumannii, we provide initial insight into the mechanism of action of a 2AI-based antibiofilm agent. Confocal microscopy confirmed that the 2AI is cell permeable, while pull-down assays identified BfmR, a response regulator that is the master controller of biofilm formation, as a target for this compound. Binding assays demonstrated specificity of the 2AI for response regulators, while computational docking provided models for 2AI-BfmR interactions. The 2AI compound studied here represents a unique small molecule scaffold that targets bacterial response regulators.}, number={49}, journal={BIOCHEMISTRY}, author={Thompson, Richele J. and Bobay, Benjamin G. and Stowe, Sean D. and Olson, Andrew L. and Peng, Lingling and Su, Zhaoming and Actis, Luis A. and Melander, Christian and Cavanagh, John}, year={2012}, month={Dec}, pages={9776–9778} }
 @article{yeagley_su_mccullough_worthington_melander_2013, title={N-Substituted 2-aminoimidazole inhibitors of MRSA biofilm formation accessed through direct 1,3-bis(tert-butoxycarbonyl)guanidine cyclization}, volume={11}, ISSN={["1477-0539"]}, DOI={10.1039/c2ob26469b}, abstractNote={Antibiotic resistance is a significant problem and is compounded by the ability of many pathogenic bacteria to form biofilms. A library of N-substituted derivatives of a previously reported 2-aminoimidazole/triazole (2-AIT) biofilm modulator was constructed via α-bromoketone cyclization with 1,3-bis(tert-butoxycarbonyl)guanidine, followed by selective substitution. Several compounds exhibited the ability to inhibit biofilm formation by three strong biofilm forming strains of methicillin resistant Staphylococcus aureus (MRSA). Additionally, a number of members of this library exhibited synergistic activity with oxacillin against planktonic MRSA. Compounds with this type of dual activity have the potential to be used as adjuvants with conventional antibiotics.}, number={1}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Yeagley, Andrew A. and Su, Zhaoming and McCullough, Kara D. and Worthington, Roberta J. and Melander, Christian}, year={2013}, pages={130–137} }
 @article{su_peng_melander_2012, title={A modular approach to the synthesis of 1,4,5-substituted-2-aminoimidazoles}, volume={53}, ISSN={["0040-4039"]}, DOI={10.1016/j.tetlet.2011.12.090}, abstractNote={Diversified 1,4,5-substituted-2-aminoimidazoles were rapidly assembled via sequential N–H insertion and Grignard addition to α-diazoesters. Lead compounds were identified as antibiotics against Gram-positive bacteria with an MIC value as low as 2 μg/mL.}, number={10}, journal={TETRAHEDRON LETTERS}, author={Su, Zhaoming and Peng, Lingling and Melander, Christian}, year={2012}, month={Mar}, pages={1204–1206} }
 @article{su_peng_worthington_melander_2011, title={Evaluation of 4,5-Disubstituted-2-Aminoimidazole-Triazole Conjugates for Antibiofilm/Antibiotic Resensitization Activity Against MRSA and Acinetobacter baumannii}, volume={6}, ISSN={["1860-7187"]}, DOI={10.1002/cmdc.201100316}, abstractNote={AbstractA library of 4,5‐disubstituted‐2‐aminoimidazole–triazole conjugates (2‐AITs) was synthesized, and the antibiofilm activity was investigated. This class of small molecules was found to inhibit biofilm formation by methicillin‐resistant Staphylococcus aureus (MRSA) at low‐micromolar concentrations; 4,5‐disubstituted‐2‐AITs were also able to inhibit and disperse Acinetobacter baumannii biofilms. The activities of the lead compounds were compared against the naturally occurring biofilm dispersant cis‐2‐decenoic acid and were revealed to be more potent. The ability of selected compounds to resensitize MRSA to traditional antibiotics (resensitization activity) was also determined. Lead compounds were observed to resensitize MRSA to oxacillin by 2–4‐fold.}, number={12}, journal={CHEMMEDCHEM}, author={Su, Zhaoming and Peng, Lingling and Worthington, Roberta J. and Melander, Christian}, year={2011}, month={Dec}, pages={2243–2251} }
 @article{peng_desousa_su_novak_nevzorov_garland_melander_2011, title={Inhibition of Acinetobacter baumannii biofilm formation on a methacrylate polymer containing a 2-aminoimidazole subunit}, volume={47}, number={17}, journal={Chemical Communications (Cambridge, England)}, author={Peng, L. L. and DeSousa, J. and Su, Z. M. and Novak, B. M. and Nevzorov, A. A. and Garland, E. R. and Melander, C.}, year={2011}, pages={4896–4898} }
 @article{reyes_huigens_su_simon_melander_2011, title={Synthesis and biological activity of 2-aminoimidazole triazoles accessed by Suzuki-Miyaura cross-coupling}, volume={9}, ISSN={["1477-0520"]}, DOI={10.1039/c0ob00925c}, abstractNote={A pilot library of 2-aminoimidazole triazoles (2-AITs) was synthesized and assayed against Acinetobacter baumannii and methicillin-resistant Staphylococus aureus (MRSA). Results from these studies show that these new derivatives have improved biofilm dispersal activities as well as antibacterial properties against A. baumannii. With MRSA biofilms they are found to possess biofilm inhibition capabilities at low micromolar concentrations.}, number={8}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Reyes, Samuel and Huigens, Robert W., III and Su, Zhaoming and Simon, Michel L. and Melander, Christian}, year={2011}, pages={3041–3049} }
 @article{su_rogers_mccall_smith_ravishankar_mullikin_melander_2010, title={A nitroenolate approach to the synthesis of 4,5-disubstituted-2-aminoimidazoles. Pilot library assembly and screening for antibiotic and antibiofilm activity}, volume={8}, number={12}, journal={Organic & Biomolecular Chemistry}, author={Su, Z. M. and Rogers, S. A. and McCall, W. S. and Smith, A. C. and Ravishankar, S. and Mullikin, T. and Melander, C.}, year={2010}, pages={2814–2822} }