In vitro anti-bacterial and time kill evaluation of binuclear tricyclohexylphosphanesilver(I) dithiocarbamates, {Cy3PAg(S2CNRR')}2

Yi Jiun Tan; Yee Seng Tan; Chien Ing Yeo; Jactty Chew; Edward R T Tiekink

doi:10.1016/j.jinorgbio.2018.12.017

In vitro anti-bacterial and time kill evaluation of binuclear tricyclohexylphosphanesilver(I) dithiocarbamates, {Cy₃PAg(S₂CNRR')}₂

J Inorg Biochem. 2019 Mar:192:107-118. doi: 10.1016/j.jinorgbio.2018.12.017. Epub 2019 Jan 6.

Authors

Yi Jiun Tan¹, Yee Seng Tan², Chien Ing Yeo², Jactty Chew³, Edward R T Tiekink⁴

Affiliations

¹ Research Centre for Crystalline Materials, School of Science and Technology, Sunway University, No. 5 Jalan Universiti, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia; Department of Biological Sciences, School of Science and Technology, Sunway University, No. 5 Jalan Universiti, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
² Research Centre for Crystalline Materials, School of Science and Technology, Sunway University, No. 5 Jalan Universiti, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
³ Department of Biological Sciences, School of Science and Technology, Sunway University, No. 5 Jalan Universiti, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: jacttyc@sunway.edu.my.
⁴ Research Centre for Crystalline Materials, School of Science and Technology, Sunway University, No. 5 Jalan Universiti, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia. Electronic address: edwardt@sunway.edu.my.

PMID: 30640150
DOI: 10.1016/j.jinorgbio.2018.12.017

Abstract

Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl₃PAg(S₂CNRR')}₂ for R = R' = Et (1), CH₂CH₂ (2), CH₂CH₂OH (3) and R = Me, R' = CH₂CH₂OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, μ₂-bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS₃ donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log₁₀ CFU/mL against S. aureus (MRSA).

Keywords: Anti-microbial; Dithiocarbamate; Phosphanesilver(I) compounds; Thiolate; Time kill assay.

MeSH terms

Anti-Bacterial Agents* / chemical synthesis
Anti-Bacterial Agents* / chemistry
Anti-Bacterial Agents* / pharmacology
Chloramphenicol / pharmacology
Coordination Complexes* / chemical synthesis
Coordination Complexes* / chemistry
Coordination Complexes* / pharmacology
Drug Evaluation, Preclinical
Methicillin-Resistant Staphylococcus aureus / growth & development*
Silver* / chemistry
Silver* / pharmacology
Thiocarbamates* / chemical synthesis
Thiocarbamates* / chemistry
Thiocarbamates* / pharmacology

Substances

Anti-Bacterial Agents
Coordination Complexes
Thiocarbamates
Silver
Chloramphenicol