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

• Main Authors: Tan, Yi Jiun *, Tan, Yee Seng *, Yeo, Chien Ing *, Chew, Jactty *, Tiekink, Edward R. T. *
• Format: Article
• Language: English
• Published: Elsevier 2019
• Subjects: QD Chemistry
• Online Access: http://eprints.sunway.edu.my/989/1/Tiekink%20In%20vitro%20JInorgBiochem%20192%20%282019%29%20107.pdf; http://eprints.sunway.edu.my/989/; http://doi.org/10.1016/j.jinorgbio.2018.12.017

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).