@article{stowe_tucker_thompson_piper_richards_rogers_mathies_melander_cavanagh_2012, title={Evaluation of the toxicity of 2-aminoimidazole antibiofilm agents using both cellular and model organism systems}, volume={35}, ISSN={["1525-6014"]}, DOI={10.3109/01480545.2011.614620}, abstractNote={Biofilm formation is a ubiquitous bacterial defense mechanism and has been shown to be a primary element in the antibiotic resistance of many human diseases, especially in the case of nosocomial infections. Recently, we have developed several compound libraries that are extremely effective at both dispersing preexisting biofilms and also inhibiting their initial formation. In addition to their antibiofilm properties, some of these molecules are able to resensitize resistant bacterial strains to previously ineffective antibiotics and are being assessed as adjuvants. In this study, we evaluated the toxic effects of three of our most effective 2-aminoimidazole compounds (dihydrosventrin, RA, and SPAR) using a rapid pipeline that combines a series of assays. A methylthiazolyldiphenyl-tetrazolium assay, using the HaCaT keratinocyte cell line was used to determine epidermal irritants and was combined with Caenorhabditis elegans fecundity assays that demonstrated the effects of environmental exposure to various concentrations of these molecules. In each case, the assays showed that the compounds did not exhibit toxicity until they reached well above their current biofilm dispersion/inhibition concentrations. The most effective antibiofilm compound also had significant effects when used in conjunction with several standard antibiotics against resistant bacteria. Consequently, it was further investigated using the C. elegans assay in combination with different antibiotics and was found to maintain the same low level of toxicity as when acting alone, bolstering its candidacy for further testing as an adjuvant.}, number={3}, journal={DRUG AND CHEMICAL TOXICOLOGY}, author={Stowe, Sean D. and Tucker, Ashley T. and Thompson, Richele and Piper, Amanda and Richards, Justin J. and Rogers, Steven A. and Mathies, Laura D. and Melander, Christian and Cavanagh, John}, year={2012}, month={Jul}, pages={310–315} }
 @article{worthington_richards_melander_2012, title={Small molecule control of bacterial biofilms}, volume={10}, number={37}, journal={Organic & Biomolecular Chemistry}, author={Worthington, R. J. and Richards, J. J. and Melander, C.}, year={2012}, pages={7457–7474} }
 @misc{stowe_richards_tucker_thompson_melander_cavanagh_2011, title={Anti-biofilm compounds derived from marine sponges}, volume={9}, number={10}, journal={Marine Drugs}, author={Stowe, S. D. and Richards, J. J. and Tucker, A. T. and Thompson, R. and Melander, C. and Cavanagh, J.}, year={2011}, pages={2010–2035} }
 @article{bunders_richards_melander_2010, title={Identification of aryl 2-aminoimidazoles as biofilm inhibitors in Gram-negative bacteria}, volume={20}, ISSN={["0960-894X"]}, DOI={10.1016/j.bmcl.2010.04.042}, abstractNote={The synthesis and biofilm inhibitory activity of a 30-member aryl amide 2-aminoimidazole library against the three biofilm forming Gram-negative bacteria Escherichia coli, Psuedomonas aeruginosa, and Acinetobacter baumannii is presented. The most active compound identified inhibits the formation of E. coli biofilms with an IC(50) of 5.2 microM and was observed to be non-toxic to planktonic growth, demonstrating that analogues based on an aryl framework are viable options as biofilm inhibitors within the 2-aminoimidazole family.}, number={12}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Bunders, Cynthia A. and Richards, Justin J. and Melander, Christian}, year={2010}, month={Jun}, pages={3797–3800} }
 @article{richards_reyes_stowe_tucker_ballard_mathies_cavanagh_melander_2009, title={Amide Isosteres of Oroidin: Assessment of Antibiofilm Activity and C. elegans Toxicity}, volume={52}, ISSN={["1520-4804"]}, DOI={10.1021/jm900378s}, abstractNote={The synthesis and antibiofilm activities of sulfonamide, urea, and thiourea oroidin analogues are described. The most active derivative was able to selectively inhibit P. aeruginosa biofilm development and is also shown to be nontoxic upward of 1 mM to the development of C. elegans in comparison to other similar isosteric analogues and the natural product oroidin.}, number={15}, journal={JOURNAL OF MEDICINAL CHEMISTRY}, author={Richards, Justin J. and Reyes, Samuel and Stowe, Sean D. and Tucker, Ashley T. and Ballard, T. Eric and Mathies, Laura D. and Cavanagh, John and Melander, Christian}, year={2009}, month={Aug}, pages={4582–4585} }
 @article{ballard_richards_aquino_reed_melander_2009, title={Antibiofilm Activity of a Diverse Oroidin Library Generated through Reductive Acylation}, volume={74}, ISSN={["0022-3263"]}, DOI={10.1021/jo802260t}, abstractNote={A diverse 20-compound library of analogues based on the marine alkaloid oroidin were synthesized via a reductive acylation strategy. The final target was then assayed for inhibition and dispersion activity against common proteobacteria known to form biofilms. This methodology represents a significant improvement over the generality of known methods to acylate substrates containing 2-aminoimidazoles and has the potential to have broad application to the synthesis of more advanced oroidin family members and their corresponding analogues.}, number={4}, journal={JOURNAL OF ORGANIC CHEMISTRY}, author={Ballard, T. Eric and Richards, Justin J. and Aquino, Arianexys and Reed, Catherine S. and Melander, Christian}, year={2009}, month={Feb}, pages={1755–1758} }
 @misc{richards_melander_2009, title={Controlling Bacterial Biofilms}, volume={10}, ISSN={["1439-7633"]}, DOI={10.1002/cbic.200900317}, number={14}, journal={CHEMBIOCHEM}, author={Richards, Justin J. and Melander, Christian}, year={2009}, month={Sep}, pages={2287–2294} }
 @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{richards_reed_melander_2008, title={Effects of N-pyrrole substitution on the anti-biofilm activities of oroidin derivatives against Acinetobacter baumannii}, volume={18}, ISSN={["0960-894X"]}, DOI={10.1016/j.bmcl.2008.06.089}, abstractNote={Bacteria of the genus Acinetobacter spp. are rapidly emerging as problematic pathogens in healthcare settings. This is exacerbated by the bacteria’s ability to form robust biofilms. Marine natural products incorporating a 2-aminoimidazole (2-AI) motif, namely from the oroidin class of marine alkaloids, have served as a unique scaffold for developing molecules that have the ability to inhibit and disperse bacterial biofilms. Herein we present the anti-biofilm activity of a small library of second generation oroidin analogues against the bacterium Acinetobacter baumannii.}, number={15}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Richards, Justin J. and Reed, Catherine S. and Melander, Christian}, year={2008}, month={Aug}, pages={4325–4327} }
 @article{richards_ballard_melander_2008, title={Inhibition and dispersion of Pseudomonas aeruginosa biofilms with reverse amide 2-aminoimidazole oroidin analogues}, volume={6}, ISSN={["1477-0539"]}, DOI={10.1039/b719082d}, abstractNote={The marine alkaloid oroidin along with a small library of reverse amide (RA) 2-aminoimidazoles were synthesized and assayed for anti-biofilm activity against PAO1 and PA14, two strains of the medically relevant γ-proteobacteriumPseudomonas aeruginosa. Analogues that contained a long, linear alkyl chain were more potent inhibitors than the natural product at preventing the formation of PAO1 and PA14 biofilms. The most active compound in the series was also shown to disperse established PAO1 and PA14 biofilms at low micromolar concentrations.}, number={8}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Richards, Justin J. and Ballard, T. Eric and Melander, Christian}, year={2008}, pages={1356–1363} }
 @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{ballard_richards_wolfe_melander_2008, title={Synthesis and Antibiofilm Activity of a Second-Generation Reverse-Amide Oroidin Library: A Structure-Activity Relationship Study}, volume={14}, ISSN={["1521-3765"]}, DOI={10.1002/chem.200801419}, abstractNote={A second-generation library of 2-aminoimidazole-based derivatives incorporating a “reversed amide” (RA) motif in comparison to the marine natural product oroidin were synthesized and subsequently assayed for antibiofilm activity against the medically relevant Gram-negative proteobacteria P. aeruginosa and A. baumannii. Most notably, an in-depth activity profile is reported for the most active subclass of derivatives that bear linear aliphatic chains off the amide bond. Additionally, further structural modifications of the core template, such as removal of the amide bond or substitution with a triazole isostere, resulted in the discovery of analogues with antibiofilm activities that varied with respect to their inhibition and dispersal properties of P. aeruginosa and A. baumannii biofilms.}, number={34}, journal={CHEMISTRY-A EUROPEAN JOURNAL}, author={Ballard, T. Eric and Richards, Justin J. and Wolfe, Amanda L. and Melander, Christian}, year={2008}, pages={10745–10761} }
 @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={A 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 gamma-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{richards_melander_2008, title={Synthesis of a 2-aminoimidazole library for antibiofilm screening utilizing the Sonogashira reaction}, volume={73}, ISSN={["0022-3263"]}, DOI={10.1021/jo800618q}, abstractNote={The divergent synthesis of a 21-member library composed of 2-aminoimidazole compounds for evaluation as novel antibiofilm molecules is presented. The Sonogashira reaction was employed with three regioisomeric aryl iodides and 11 different alkynes to generate variously substituted diverse ring systems. Good to excellent yields (80-97%) for the reaction were obtained, and the products provide adequate handles for further manipulation into more advanced analogues.}, number={13}, journal={JOURNAL OF ORGANIC CHEMISTRY}, author={Richards, Justin J. and Melander, Christian}, year={2008}, month={Jul}, pages={5191–5193} }
 @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-} }