05/16/2022
By Kwok Fan Chow
The Kennedy College of Science, Department of Chemistry, invites you to attend a research proposal defense by Dang V. Troung entitled “Antimicrobial Activities of Gold Compounds and the Underlying Mechanism.” The defense will be held virtually on Friday, May 20 at 1 p.m.
Committee Chair: Prof. Mingdi Yan, Department of Chemistry, University of Massachusetts Lowell
Committee Members:
- Prof. Olof Ramstrom, Department of Chemistry, University of Massachusetts Lowell
- Prof. Matthew J. Gage, Department of Chemistry, University of Massachusetts Lowell
- Prof. Guixin He, Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell
Abstract:
Due to the inappropriate usage and prescription of antibiotics, global communities and healthcare system are facing critical challenge of antibiotic resistance development. With limited new development of antimicrobial agents from private industry and pharmaceuticals, researcher and government agency employ drug repurposing strategy to reduce the time and cost of development. Auranofin has shown enhancement in bactericidal activity against Gram-positive but limited effect against Gram-negative bacteria. My research proposed new strategies to enhance auranofin’s antimicrobial activity by either in dosage combination with thiourea or structural modification. Collected data suggested that auranofin in combination with 7mM of thiourea enhanced its antimicrobial activity at least 32-fold change increasement. Additionally, 2-mercaptoethanol trimethylphosphine gold (I) complex (MS-40/auranofin analog) also exhibited great antimicrobial activities even against multidrug resistance bacteria. The combination of AF/TU or structural modification in MS-40 allowed AF to overcome the membrane barrier and efflux regulation of Gram-negative bacteria. Additional antibacterial mechanisms included a potent inhibition of bacteria thioredoxin reductase (TrxR, AF/TU IC50 of 0.003 µg/mL and MS-40 IC50 of 0.004 µg/mL), and Cu(I) regulation interference.