@article{worthington_rogers_huigens_melander_ritchie_2012, title={Foliar-Applied Small Molecule that Suppresses Biofilm Formation and Enhances Control of Copper-Resistant Xanthomonas euvesicatoria on Pepper}, volume={96}, ISSN={["1943-7692"]}, DOI={10.1094/pdis-02-12-0190-re}, abstractNote={ We report a small molecule additive, a member of the 2-aminoimidazole (2AI) group that is an analogue of the marine sponge natural product oroidin that suppresses resistance of Xanthomonas euvesicatoria to copper and decreases biofilm formation in an in vitro system. In laboratory experiments, 2AI combined with copper reduced both bacterial multiplication in broth and bacterial recovery on pepper leaf discs of a copper-resistant strain of X. euvesicatoria to a level close to that of a copper-sensitive strain. Compound 2AI used alone exhibited minimal bactericidal activity. In 3 years of field experiments, when combined with a copper-containing material, copper hydroxide (Kocide 3000), and other antibacterial materials, these spray mixtures resulted in decreased bacterial spot foliar disease and increased fruit yields using hybrid bell pepper (Capsicum annuum) cultivars and copper-resistant strains of X. euvesicatoria. This study demonstrates the concept for using small molecules as additives to antibacterial compounds at nonbactericidal concentrations under field conditions that, in the laboratory, were demonstrated to suppress bacterial biofilms and copper-resistant strains. }, number={11}, journal={PLANT DISEASE}, author={Worthington, R. J. and Rogers, S. A. and Huigens, R. W., III and Melander, C. and Ritchie, D. F.}, year={2012}, month={Nov}, pages={1638–1644} }
 @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{reed_huigens_rogers_melander_2010, title={Modulating the development of E. coli biofilms with 2-aminoimidazoles}, volume={20}, ISSN={["0960-894X"]}, DOI={10.1016/j.bmcl.2010.08.075}, abstractNote={The synthesis of a 20 member 2-aminoimidazole/triazole pilot library is reported. Each member of the library was screened for its ability to inhibit or promote biofilm development of either Escherichia coli and Acinetobacter baumannii. From this screen, E. coli-selective 2-aminoimidazoles were discovered, with the best inhibitor inhibiting biofilm development with an IC50 of 13 μM. The most potent promoter of E. coli biofilm formation promoted biofilm development by 321% at 400 μM.}, number={21}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Reed, Catherine S. and Huigens, Robert W., III and Rogers, Steven A. and Melander, Christian}, year={2010}, month={Nov}, pages={6310–6312} }
 @article{rogers_huigens_cavanagh_melander_2010, title={Synergistic Effects between Conventional Antibiotics and 2-Aminoimidazole-Derived Antibiofilm Agents}, volume={54}, ISSN={["0066-4804"]}, DOI={10.1128/aac.01418-09}, abstractNote={ABSTRACT
          
            2-Aminoimidazoles are an emerging class of small molecules that possess the ability to inhibit and disperse biofilms across bacterial order, class, and phylum. Herein, we report the synergistic effect between a 2-aminoimidazole/triazole conjugate and antibiotics toward dispersing preestablished biofilms, culminating with a 3-orders-of-magnitude increase of biofilm dispersion toward
            Staphylococcus aureus
            biofilms. Furthermore, we document that the 2-aminoimidazole/triazole conjugate will also resensitize multidrug-resistant strains of bacteria to the effects of conventional antibiotics, including methicillin-resistant
            Staphylococcus aureus
            (MRSA) and multidrug-resistant
            Acinetobacter baumannii.
          }, number={5}, journal={ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}, author={Rogers, Steven A. and Huigens, Robert W., III and Cavanagh, John and Melander, Christian}, year={2010}, month={May}, pages={2112–2118} }
 @article{rogers_huigens_melander_2009, title={A 2-Aminobenzimidazole That Inhibits and Disperses Gram-Positive Biofilms through a Zinc-Dependent Mechanism}, volume={131}, ISSN={["0002-7863"]}, DOI={10.1021/ja9024676}, abstractNote={A number of 2-aminobenzimidazole derivatives were synthesized and screened for their ability to inhibit and disperse bacterial biofilms. From these compounds, a lead 2-aminobenzimidazole was identified that both inhibited and dispersed MRSA, vancomycin-resistant Enterococcus faecium, and Staphylococcus epidermidis biofilms. Mechanistic studies showed that the activity is Zn(II)-dependent, potentially via a direct zinc-chelating mechanism.}, number={29}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Rogers, Steven A. and Huigens, Robert W., III and Melander, Christian}, year={2009}, month={Jul}, pages={9868-+} }
 @article{melander_moeller_ballard_richards_huigens_cavanagh_2009, title={Evaluation of dihydrooroidin as an antifouling additive in marine paint}, volume={63}, ISSN={["0964-8305"]}, DOI={10.1016/j.ibiod.2008.08.009}, abstractNote={Methods used to deter biofouling of underwater structures and marine vessels present a serious environmental issue and are both problematic and costly for government and commercial marine vessels worldwide. Current antifouling methods include compounds that are toxic to aquatic wildlife and marine ecosystems. Dihydrooroidin (DHO) was shown to completely inhibit Halomonas pacifica biofilms at 100 μM in a static biofilm inhibition assay giving precedence for the inhibition of other marine biofilm-forming organisms. Herein we present DHO as an effective paint-based, non-cytotoxic, antifouling agent against marine biofouling processes in a marine mesocosm.}, number={4}, journal={INTERNATIONAL BIODETERIORATION & BIODEGRADATION}, author={Melander, Christian and Moeller, Peter D. R. and Ballard, T. Eric and Richards, Justin J. and Huigens, Robert W., III and Cavanagh, John}, year={2009}, month={Jun}, pages={529–532} }
 @article{huigens_rogers_steinhauer_melander_2009, title={Inhibition of Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa biofilm formation with a class of TAGE-triazole conjugates}, volume={7}, ISSN={["1477-0539"]}, DOI={10.1039/b817926c}, abstractNote={A chemically diverse library of TAGE-triazole conjugates was synthesized utilizing click chemistry on the TAGE scaffold. This library of small molecules was screened for anti-biofilm activity and found to possess the ability of inhibiting biofilm formation against Acinetobacter baumannii, Staphylococcus aureus and Pseudomonas aeruginosa. One such compound in this library demonstrated the most potent inhibitory effect against Staphylococcus aureus biofilm formation that has been displayed by any 2-aminoimidazole derivative.}, number={4}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Huigens, Robert W., III and Rogers, Steven A. and Steinhauer, Andrew T. and Melander, Christian}, year={2009}, pages={794–802} }
 @article{huigens_reyes_reed_bunders_rogers_steinhauer_melander_2010, title={The chemical synthesis and antibiotic activity of a diverse library of 2-aminobenzimidazole small molecules against MRSA and multidrug-resistant A. baumannii}, volume={18}, ISSN={["1464-3391"]}, DOI={10.1016/j.bmc.2009.12.003}, abstractNote={Multidrug-resistant bacterial infections continue to be a rising global health concern. Herein is described the development of a class of novel 2-aminobenzimidazoles with antibiotic activity. These active 2-aminobenzimidazoles retain their antibiotic activity against several strains of multidrug-resistant Staphylococcus aureus and Acinetobacter baumannii when compared to susceptible strains.}, number={2}, journal={BIOORGANIC & MEDICINAL CHEMISTRY}, author={Huigens, Robert W., III and Reyes, Samuel and Reed, Catherine S. and Bunders, Cynthia and Rogers, Steven A. and Steinhauer, Andrew T. and Melander, Christian}, year={2010}, month={Jan}, pages={663–674} }
 @article{huigens_ma_gambino_moeller_basso_cavanagh_wozniak_melander_2008, title={Control of bacterial biofilms with marine alkaloid derivatives}, volume={4}, ISSN={["1742-2051"]}, DOI={10.1039/b719989a}, abstractNote={Bacterial biofilms are defined as a community of surface-attached bacteria that are protected by an extracellular matrix of biomolecules. We have recently reported the synthesis of a small molecule, denoted TAGE, based on the natural product bromoageliferin and demonstrated that TAGE has anti-biofilm activity against Pseudomonas aeruginosa. Herein we demonstrate that TAGE: (1) does not have selective toxicity against cells within the biofilm state, (2) will inhibit biofilm development under flow conditions, indicating that the CV staining protocol correlates with the ability to be active under biomimetic conditions, and (3) will disperse preformed P. aeruginosa biofilms. We also present preliminary toxicity work that indicates that TAGE is devoid of cytotoxicity in rat and mice cell lines. Advanced derivatives of TAGE have generated compounds shown to be exceedingly effective as biofilm inhibitors against the gamma-proteobacteria in this study (P. aeruginosa strains PAO1, PA14, PDO300, and Acinetobacter baumannii). TAGE derivatives also possessed anti-biofilm activity against the beta-proteobacterium Bordetella bronchiseptica (Rb50) and the Gram-positive bacterium Staphylococcus aureus;TAGE derivatives inhibited the formation of biofilms, however, some of this activity is attributed to microbicidal activity. The TAGE derivatives presented in this study, however, do not disperse pre-formed biofilms with the same efficiency as TAGE.}, number={6}, journal={MOLECULAR BIOSYSTEMS}, author={Huigens, Robert W., III and Ma, Luyan and Gambino, Christopher and Moeller, Peter D. R. and Basso, Anne and Cavanagh, John and Wozniak, Daniel J. and Melander, Christian}, year={2008}, pages={614–621} }
 @article{richards_huigens_ballard_basso_cavanagh_melander_2008, title={Inhibition and dispersion of proteobacterial biofilms}, number={14}, journal={Chemical Communications (Cambridge, England)}, author={Richards, J. J. and Huigens, R. W. and Ballard, T. E. and Basso, A. and Cavanagh, J. and Melander, C.}, year={2008}, pages={1698–1700} }
 @article{richards_ballard_huigens_melander_2008, title={Synthesis and screening of an oroidin library against Pseudomonas aeruginosa biofilms}, volume={9}, ISSN={["1439-4227"]}, DOI={10.1002/cbic.200700774}, abstractNote={AbstractA 50‐compound library based on the marine natural product oroidin was synthesized and assayed for anti‐biofilm activity against PAO1 and PA14, two strains of the medically relevant γ‐proteobacterium Pseudomonas aeruginosa. Through structure–activity relationship (SAR) analysis of analogues based on the oroidin template, several conclusions can be drawn as to what structural properties of the synthetic derivatives are necessary to elicit a biological response. Notably, the most active analogues identified were those that contained a 2‐aminoimidazole (2‐AI) motif and a dibrominated pyrrolecarboxamide subunit. Here we disclose the synthesis and subsequently determined biological activity of this unique class of compounds as inhibitors of biofilm formation that have no direct antibiotic effect.}, number={8}, journal={CHEMBIOCHEM}, author={Richards, Justin J. and Ballard, T. Eric and Huigens, Robert W., III and Melander, Christian}, year={2008}, month={May}, pages={1267–1279} }
 @article{huigens_richards_parise_ballard_zeng_deora_melander_2007, title={Inhibition of Pseudomonas aeruginosa biofilm formation with bromoageliferin analogues}, volume={129}, number={22}, journal={Journal of the American Chemical Society}, author={Huigens, R. W. and Richards, J. J. and Parise, G. and Ballard, T. E. and Zeng, W. and Deora, R. and Melander, C.}, year={2007}, pages={6966-} }