Potential antibacterial and antifungal activities of novel sulfamidophosphonate derivatives bearing the quinoline or quinolone moiety

A series of new alpha-sulfamidophosphonate/sulfonamidophosphonate (4a-n) and cyclosulfamidophosphonate (5a-d) derivatives containing the quinoline or quinolone moiety was designed and synthesized via Kabachnik-Fields reaction in the presence of ionic liquid under ultrasound irradiation. This efficient methodology provides new 1,2,5-thiadiazolidine-1,1-dioxide derivatives 5a-d in one step and optimal conditions. The molecular structures of the novel compounds 4a-n and 5a-d were confirmed using various spectroscopic methods. All these compounds were evaluated for their in vitro antibacterial activity against Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and Gram-positive (Staphylococcus aureus ATCC 27923) bacteria, in addition to three clinical strains (E. coli 1, P. aeruginosa 1, and S. aureus 1). Most of the tested compounds showed more potent inhibitory activities against both Gram-positive and -negative bacteria compared with the sulfamethoxazole reference. The following compounds, 4n, 4f, 4g, 4m, 4l, 4d, and 4e, are the most active sulfamidophosphonate derivatives. Furthermore, these molecules gave interesting zones of inhibition varying between 28 and 49 mm, against all tested bacterial strains, with a low minimum inhibitory concentration (MIC) value ranging from 0.125 to 8 mu g/ml. All the synthesized derivatives were also evaluated for their in vitro antifungal activity against Fusarium oxyporum f. sp. lycopersici and Alternaria sp. The results revealed that all the synthesized compounds exhibited excellent antifungal inhibition and the compounds 4f, 4g, 4m, and 4i were the most potent derivatives with MIC values ranging from 0.25 to 1 mu g/ml against the two tested fungal strains. The strongest inhibition of bacteria and fungi strains was detected by the effect of quinolone and sulfamide moieties.

Automated summary

A series of new alpha-sulfamidophosphonate/sulfonamidophosphonate and cyclosulfamidophosphonate derivatives were designed and synthesized, showing potent inhibitory activities against both Gram-positive and -negative bacteria as well as excellent antifungal inhibition. The most active derivatives exhibited low minimum inhibitory concentrations and interesting zones of inhibition, highlighting the potential of these compounds for further applications.