Antimicrobial activity of pyrimidinophanes with thiocytosine and uracil moieties

• DOI: 10.1016/j.ejmech.2011.05.034
• Publication Date: 2011-05-23T00:38:23Z
• Authors: Vyacheslav E. Sem...; Anatoly S. Mikhailov; Alexandra D. Volo...; Natalia V. Kulik; Alexandra D. Niki...; Vladimir V. Zobov; Sergey V. Kharlamov; Shamil K. Latypov; Vladimir S. Reznik
• Keywords: Cytosine; Spectrometry, Mass, Electrospray Ionization; Magnetic Resonance Spectroscopy; Pyrimidines; Animals; Microbial Sensitivity Tests; Uracil; 01 natural sciences; Anti-Bacterial Agents; 3. Good health; 0104 chemical sciences

Reactions of pyrimidinophanes with two 6-methylthiocytosine and one 5(6)-alkyluracil moieties bridged with each other by polymethylene spacers with methyl or nonyl p-toluenesulfonate, p-toluenesulfonic acid, methanesulfonate and trifluorosulfonate afforded amphiphilic macrocyclic bis-p-toluene-, methane- and trifluorosulfonates. Despite the presence of several reaction centers in the initial pyrimidinophane molecules, protonation and methylation occurred only at the N(1) atom (with quaternization) of the 6-methylthiocytosine moieties. The bacteriostatic and fungistatic activity of the products was estimated. Macrocyclic tosylates exhibit a remarkable selectivity towards Staphylococcus aureus, with MIC values comparable with a reference drug. Bacteriostatic activity of the amphiphilic pyrimidinophanes depends on the size of the macrocycles, and the highest activity corresponds to definite lengths of polymethylene bridges. Besides, the antimicrobial activity of the screened pyrimidine derivatives depends on their topology. While macrocyclic tosylates are more active against bacteria than against fungi, acyclic tosylate with the same structural fragments shows a dramatical decrease of MIC towards mold and yeast with respect to the corresponding macrocycle. It is found that macrocyclic and acyclic tosylates in high dilutions decrease the extracellular lipase activity.