Synthesis and antimicrobial activity of pyrimidinophanes with two uracil units and bridging nitrogen atoms

Abstract

A series of pyrimidinophanes containing two uracil units and nitrogen atoms in bridging polymethylene chains –(CH2) n N(Et)(CH2) m – (n, m = 5, 6) have been synthesized. The uracil moieties are represented by 6-methyl-, 5-decyl-6-methyl-, and 5-fluorouracils. Quaternization of the bridging N atom with ethylbromide or n-decylbromide yielded amphiphilic pyrimidinophanes, which were evaluated for their antibacterial and antifungal activity in terms of minimal inhibiting concentration (MIC) against Gram-positive and Gram-negative bacteria and fungi. It has been found that MICs of the amphiphilic pyrimidinophanes decrease with increasing lipophilicity of the alkyl substituents at the bridging N atoms and with increasing polymethylene N(pyr)–N chain length (in some cases MIC against Staphylococcus aureus is below 1 ig/mL). The MICs increase dramatically upon introduction of lipophilic n-decyl substituents at C(5) atoms of the uracil moiety. The results can be used in the search for new highly effective antimicrobial agents.