In vitro antibacterial and time-kill evaluation of phosphanegold(I) dithiocarbamates, R3PAu[S2CN(iPr)CH2CH2OH] for R = Ph, Cy and Et, against a broad range of Gram-positive and Gram-negative bacteria

Jiun-Horng Sim,Nazzatush Shimar Jamaludin,Yoke-Kqueen Cheah,Chai-Hoon Khoo,Edward R T Tiekink,Hoi-Ling Seng,Siti Nadiah Binti Abdul Halim

doi:10.1007/s13404-014-0144-y

Jiun-Horng Sim, Nazzatush Shimar Jamaludin + Show 5 more

Open Access

https://doi.org/10.1007/s13404-014-0144-y

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Journal: Gold Bulletin	Publication Date: Oct 1, 2014
Citations: 56	License type: CC BY 4.0

Affiliation: Universiti Putra Malaysia, University of Malaya

Abstract

The in vitro antibacterial activity of a series of phosphanegold(I) dithiocarbamates, R3PAu[S2CN(iPr)CH2CH2OH] where R = Ph (2), Cy (3) and Et (4), against 25 strains of Gram-positive and Gram-negative bacteria were determined through the disk diffusion method, the determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and by time-kill assay. Compounds 2 and 3 have been shown to be specifically active against the tested Gram-positive bacteria, with MIC values ranging from 7.81 to 125 μg/ml. Compound 4 has a broad-spectrum activity against 24 strains of Gram-positive and Gram-negative bacteria, with MIC values ranging from 0.98 to 1,000 μg/ml. Noteworthy was that 4, with a very low MIC value of 0.98 μg/ml, is particularly effective against methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus sp., as effective as the standard antibiotic ciprofloxacin. In time-kill studies, the bacteriostatic and bactericidal activities of the tested compounds towards susceptible strains were similar to their characteristics determined by MBC/MIC ratios. In the time-kill assay, 2 and 3 showed only bactericidal activity towards the susceptible strains tested, whereas 4 revealed varying degrees of bactericidal and bacteriostatic activities, results indicating different antibacterial mechanisms are involved.

Highlights

The emergence of resistance in pathogenic bacteria to multiple antibacterial agents has become a significant public health issue as there are fewer, or even sometimes no, effective antibiotic treatments available for these infectious diseases [1]; see recent commentaries on this issue [2, 3]
As a case in point, over time, the original Gram-positive bacterium Staphylococcus aureus developed resistance towards a series of first-line, second-line and even third-line antibiotics [6] to evolve into methicillin-resistant S. aureus (MRSA)
The R3PAu[S2CN(iPr)CH2CH2OH] compounds, where R = Ph (2), Cy (3) and Et (4), and sodium dithiocarbamate salt (1), became available in an earlier study describing their cytotoxicity against MCF-7R breast cancer cells and their differing pathways of causing cell death, i.e. apoptopic for 2 and

Summary

Introduction

The emergence of resistance in pathogenic bacteria to multiple antibacterial agents has become a significant public health issue as there are fewer, or even sometimes no, effective antibiotic treatments available for these infectious diseases [1]; see recent commentaries on this issue [2, 3]. The antibacterial activity of 1–4 were quantitatively assessed by determining their minimum inhibitory concentration (MIC) values and the results are tabulated in Table 2; a lower MIC value indicates a better antimicrobial agent as less compound is required to inhibit growth of the bacteria. The MIC values of compounds 2–4 were in the range 0.98– 2,000.00 μg/ml, whereas ciprofloxacin was active in the range of 0.06–125.00 μg/ml, tetracycline in the range of 1.95– 250.00 μg/ml and chloramphenicol in the range of 62.50– 250.00 μg/ml towards susceptible tested bacteria.

Results

Conclusion