New diaryl ω-(isothiocyanato)alkylphosphonates and their mercapturic acids as potential antibacterial agents

Abstract

Thirty-four novel, diaryl ω-(isothiocyanato)alkylphosphonates with chlorine atom and methoxy, dimethoxy, methylsulfanyl, or methoxycarbonyl groups at ortho, meta, or para positions of the phenyl ring, and with an unbranched alkyl chain (n = 2–6) were designed and synthesized in a one-pot reaction in 11–76% yields. All isothiocyanates thus generated were evaluated for the first time for antibacterial activity on Pseudomonas aeruginosa and Staphylococcus aureus bacterial strains, and had satisfactory antibacterial activity in most cases. The highest activity, similar to that of reference gentamicin activity against S. aureus, was seen in compounds 9 and 13 (1.5 ± 0.1 and 2.5 ± 0.2 μM, respectively), whereas for P. aeruginosa more than half of tested compounds proved to be more effective than gentamicin. Additionally, selected isothiocyanates (9, 13, 18, and 23) were transformed in 52–73% yields into mercapturic acids 42–45, which also exhibited satisfactory antibacterial effect against S. aureus strain.