Synthesis and biological activity of salinomycin conjugates with floxuridine

Screening a Commercial Library of Pharmacologically Active Small Molecules against Staphylococcus aureus Biofilms

“…The antimicrobial activity of gemcitabine against several strains of S. aureus has previously been reported by Jordheim et al (18). An average MIC of 0.9 M was reported in that study for most clinical MRSA strains, and that finding agrees very well with our observation of an IC 50 below 0.6 M. Huczynski et al (19) reported on the antimicrobial activity of floxuridine and several conjugates against several reference and clinical strains of S. aureus. In their studies, they found that floxuridine alone was very effective against all the strains tested, reporting an MIC equal to or below 0.016 M. In our experiments, we observed an IC 50 well below 0.6 M for floxuridine.…”

“…In their studies, they found that floxuridine alone was very effective against all the strains tested, reporting an MIC equal to or below 0.016 M. In our experiments, we observed an IC 50 well below 0.6 M for floxuridine. Unfortunately, this activity correlates with the cytotoxicity of the drug, likely making it unsuitable for repurposing (19). Gieringer et al (20) determined that 5-fluorouracil could inhibit the growth of S. aureus at an MIC of 6.15 M, which was greater than the IC 50 of 0.6 M that we observed.…”

Synthesis and antiproliferative activity of new bioconjugates of Salinomycin with amino acid esters

“…6 What is important, the compounds obtained show very interesting biological activity, including high anticancer activity and selectivity. 6 Furthermore, different SAL bioconjugates with floxuridine, 7 Cinchona alkaloids 8 and silybin 9 have been synthesized. Results of the anticancer activity tests of these bioconjugates, especially floxuridine bioconjugates, have clearly shown that this type connection of SAL with other biologically active substances leads to the formation of interesting compounds, which may be used in the nearest future in the fight against cancer.…”

“…Results of the anticancer activity tests of these bioconjugates, especially floxuridine bioconjugates, have clearly shown that this type connection of SAL with other biologically active substances leads to the formation of interesting compounds, which may be used in the nearest future in the fight against cancer. [7][8][9] However, to the best of our knowledge, no attempts have been made to synthesize SAL bioconjugates with amino acid esters. The synthesis of the compounds of this type is very interesting, because it is well known that the use of amino acid prodrugs and their derivatives improves poor solubility, poor permeability, sustained release, intravenous delivery, drug targeting as well as metabolic stability of the parent substances.…”

“…Only the ester of SAL with floxuridine is characterized by improved values of these parameters. [7][8][9] It is worth noting that up to now, amide of SAL with L- Table 1 Anticancer activity of SAL and its bioconjugates (1)(2)(3)(4)(5) The IC 50 value is defined as the concentration of a compound that corresponds to a 50% growth inhibition. Human colon adenocarcinoma cell line (LoVo) and doxorubicin-resistant subline (LoVo/DX); Human biphenotypic myelomonocytic leukemia cell line (MV4-11); normal murine embryonic fibroblast cell line (BALB/3T3).…”