
Soong Wei Si
- Antimicrobial resistance (AMR) is considered as one of the leading health threats in the public.
- AMR happens when the drug becomes ineffective or less effective against the bacterial infections due to the rapid change in permeability, enzyme modification or alteration in the target site of bacteria.
- According to the WHO (2017), methicillin-resistant Staphylococcus aureus (MRSA) is classified as one of the high-priority pathogens that require urgent counteraction with novel antibiotics.
Phosphanegold(I) thiolate compounds
- Structurally mimic auranofin
- Phosphine and thiolate ligand bind to the gold centre
- Inhibit thioredoxin reductase enzyme in MRSA

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- To study the antibacterial activity of phosphanegold(I) thiolate compounds on MRSA.
- To investigate the synergistic effect of phosphanegold(I) thiolate compounds with chloramphenicol against MRSA.
Chloramphenicol
- Effectively inhibit MRSA growth.
- Blocking protein synthesis.
- Cause dose-related bone marrow suppression.

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- Phosphanegold(I) thiolate compounds (AAu1-3 compounds), chloramphenicol and gold precursor were potent against MRSA with the MIC values found to be 3.125-6.25 µg/mL, 6.25 µg/mL and 6.25 µg/mL, respectively.
- The MBC/MIC values of less than or equal 4 indicated that these compounds were bactericidal and worked well in killing the MRSA population.
- In contrast, MRSA was not susceptible to thiolate ligands (L1-3) as the bacterial growth could be observed at all the concentrations tested, thus the MIC and MBC values were more than 100µg/mL.

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- Antibacterial effect of the compounds was strongly associated with the gold centre in the compounds.
- Precursor that does not have the ligand structure, can still exhibit its antibacterial potential against MRSA.
- Thiolate ligands that do not consist of the gold centre in their chemical structure, were inactive when tested on MRSA.

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- AAu1 and AAu3 compounds were more effective than AAu2.
- They can inhibit MRSA growth at a lower concentration.
- Variation in the R-groups might lead to a differential bioactivity in inhibiting the MRSA growth.
- Structure-activity relationships in the phosphanegold(I) thiolate compounds can be investigated in future.

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- Phosphanegold(I) thiolate compounds + chloramphenicol did not significantly increase their inhibitory efficacy against MRSA.
- The reason for the lack of positive interactions remains unclear.
- The presence of chloramphenicol led to a reduction in MIC values for the phosphanegold(I) thiolate compounds by at least one concentration.

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I would like to express my sincere gratitude to my supervisor, Assoc. Prof. Dr. Chew Jactty and Ms. Clariss Goh for their guidance and advices through the research.