Research Interests keywords:

Antimicrobials; small molecule/protein interactions; bioconjugation; reaction discovery; medicinal chemistry; organic synthesis

Research Interests:

Antimicrobial resistance is a global health crisis. The production of novel antibiotics and antifungals are insufficient to address the rapid increase in antimicrobial resistance infections. Our group is interested in approaching this problem in two ways. We are interested in the discovery and development of compounds with antibacterial or antifungal activity, and alternative approaches to the treatment or prevention of microbial infections through interrupting pathogenesis.

Students Opportunities

• There are multiple opportunities available for Brock University undergraduates. For further enquiries: Email Dr. Dustin Duncan
• We are actively recruiting MSc and PhD students through Brock University’s M.Sc. and PhD programs in Chemistry.
• Prospective postdoctoral candidates should send their CVs and a description of their research interests.

PUBLICATIONS

Journal articles

• Iyer, K.R., Li, S.C., Revie, N.M., Lou, J.W., Duncan, D., Fallah, S., Sanchez, H., Skulska, I., Mattiazzi Ušaj, M., Safizadeh, H., Larsen, B., Wong, C.,Aman, A., Kiyota, T., Yoshimura, M., Kimura, H., Hirano, H., Yoshida, M., Osada, H., Gingras, A-C., Andes, D.R., Shapiro, R.S., Robbins, N., Mazhab-Jafari, M.T., Whitesell, L., Yashiroda, Y., Boone, C., and Cowen, L.E., Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity. Cell Chem Biol, (Accepted)
• Puumala, E., Zaslaver, O., Chen, A., Duncan, D., Fogal, M., Shapiro, R., Mazhab-Jafari, M.T., Whitesell, L., Montenegro-Burke, J.R., Robbins, N., Cowen, L.E., The tri-substituted isoxazole MMV688766 exerts broad-spectrum activity against drug-resistant fungal pathogens through inhibition of lipid homeostasis. mBio, 13(6), e02730-22 (2022), DOI: 10.1128/mbio.02730.
• Kim, S.H., Steere, L., Zhang, Y-K., McGregor, C., Hahne, C., Zhou, Y., Liu, C., Cai, Y., Zhou, H., Chen, X., Puumala, E., Duncan, D., Wright, G., Liu, C. T., Whitesell, L., Cowen, L.E., Inhibiting C-4 methyl sterol oxidase with novel diazaborines to target fungal plant pathogens. ACS Chem Biol, 17(6), 1343 – 1350 (2022), DOI: 10.1021/acschembio.2c00257.
• Duncan, D., Auclair, K., Itaconate: an antimicrobial metabolite of macrophages. Can J Chem, 100(2), 104 – 113 (2022), DOI: 10.1139/cjc-2021-0117.
• Kaabel, S., Therien, J.P.D., Deschênes, C.E., Duncan, D., Friščić, T., Auclair, K., Clean enzymatic depolymerization of highly crystalline polyethylene terephthalate in moist-solid reaction mixtures. Proc Nat Acad Sci USA, 118(29), e2026452118 (2021), DOI: 10.1073/pnas.2026452118.
• Duncan, D., Lupien, A., Behr, M., Auclair, K., Effect of pH on the antimicrobial activity of the macrophage metabolite itaconate. Microbiol, 167(5), 001050 (2021), DOI: 1099/mic.0.001050.
• Guan, J., Spry, C., Tjhin, E.T, Yang, P., Kittikool, T., Howieson, V.M., Ling, H., Starrs, L., Duncan, D., Burgio, G., Saliba, K.J., Auclair, K., Exploring heteroaromatic rings as a replacement for the labile amide of antiplasmodial pantothenamides. J Med Chem, 64(8), 4478 – 4497 (2021), DOI: 1021/acs.jmedchem.0c01755.
• Swain, A., Bambouskova, M., Kim, H., Andhey, P.S., Duncan, D., Auclair, K., Chubukov, V., Simons, D.M., Roddy, T.P., Stewart, K.M., Artyomov, M.N., Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat Metab, 2, 594 – 602 (2020), DOI: 1038/s42255-020-0210-0.
• Duncan, D., Auclair. K., The coenzyme A biosynthetic pathway: a new tool for prodrug activation. Arch Biochem Biophys, 672, 108069 (2019), DOI: 10.1016/j.abb.2019.108069.
• Bambouskova, M., Gorvel, L., Lampropoulou, V., Sergushichev, A., Loginicheva, E., Johnson, K., Korenfeld, D., Mathyer, M.E., Kim, H., Huang, L-H., Duncan, D., Bregman, H., Keskin A., Santeford, A., Apte, R.S., Sehgal, R., Johnson, B., Amarasinghe, G.K., Soares, M.P., Satoh, T., Akira, S., Hai, T., de Guzman Strong, C., Auclair, K., Roddy, T.P., Biller, S.A., Jovanovic, M., Klechevsky, E., Stewart, K.M., Randolph, G.J., Artyomov, M.N., Electrophilic stress induced by dimethyl itaconate regulates IκBζ-mediated inflammatory responses. Nature, 556, 501 – 504 (2018), DOI: 10.1038/s41586-018-0052-z.
• Hammerer, F., Chang, J., Duncan, D., Castaneda Ruiz, A., Auclair, K., Small molecule restores itaconate sensitivity in Salmonella enterica: A potential new approach to treating bacterial infections. ChemBioChem, 17(16), 1513 – 1517 (2016), DOI: 10.1002/cbic.201600078.
• Bowie, D., Parvizi, P., Duncan, D., Nelson, C.J., Fyles, M., Chemical-genetic identification of the biochemical targets of polyalkyl guanidinium biocides. Org Biomol Chem, 11, 4359 – 4366 (2013), DOI: 10.1039/C3OB40593A.
• Iyer, K.R., Li, S.C., Revie, N.M., Lou, J.W., Duncan, D., Fallah, S., Sanchez, H., Skulska, I., Mattiazzi Ušaj, M., Safizadeh, H., Larsen, B., Wong, C.,Aman, A., Kiyota, T., Yoshimura, M., Kimura, H., Hirano, H., Yoshida, M., Osada, H., Gingras, A-C., Andes, D.R., Shapiro, R.S., Robbins, N., Mazhab-Jafari, M.T., Whitesell, L., Yashiroda, Y., Boone, C., and Cowen, L.E., Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity. Cell Chem Biol, 30(7), 795 – 810 (2023), DOI: 10.1016/j.chembiol.2023.06.005
• Marques, L., Lee, Y., Duncan, D., Whitesell, L., Cowen, L.E., Quave, C.L., Potent antifungal activity of pentagalloyl glucose against drug-resistant Candida albicans, Candida auris, and other non-albicans Candida species. ACS Infect Dis. 9(9), 1685 – 1694, DOI: 10.1021/acsinfecdis.3c00113
• Fallah, S., Duncan, D., Reichl, K., Smith, M., Wang, W., Porco Jr, J., Brown, L., Whitesell, L., Robbins, N., Cowen, L.E., A chemical screen identifies structurally-diverse metal chelators with activity against the fungal pathogen Candida albicans, Microbiol Spectr, 12(4), e04095-23, (2024). DOI: 10.1128/spectrum.04095.
• Patel, D., Huma, Z., Duncan, D., Reversible Covalent Inhibition – Desired Covalent Adduct Formation by Mass Action. ACS Chem Biol, 19(4), 824 – 838, (2024). DOI: 10.1021/acschembio.3c00805.
• The Atomwise AIMS Program, AI is a Viable Alternative to High Throughput Screening: a 318-Target Study. Sci. Rep. 14, 7526 (2024). DOI: 10.1038/s41598-024-54655-z

Book Chapters

• Jones, M.R., Duncan, D., Storr, T., Chapter 1: Introduction to Ligand Design in Medicinal Inorganic Chemistry, Ligand Design in Medicinal Inorganic Chemistry, Wiley Publishing, 2014.

CHEM 1P91: Chemical Principles and Properties I

CHEM 2P20: Principles of Organic Chemistry I

CHEM 3P20: Structure and Reactivity of Organic Molecules

CHEM 3P63: Indigenous Medicine and Medicinal Chemistry

CHEM 4P21: Organic Reactions and Synthesis

CHEM 5P21: Advanced Organic Synthesis