Search

The rapid increase in the antibiotic resistance of microorganisms, capable of causing diseases in humans as destroying cultural heritage sites, is a great challenge for modern science. In this regard, it is necessary to develop fundamentally novel and highly active compounds. In this study, a series of N4-alkylcytidines, including 5- and 6-methylcytidine derivatives, with extended alkyl substituents, were obtained in order to develop a new generation of antibacterial and antifungal biocides based on nucleoside derivatives. It has been shown that N4-alkyl 5- or 6-methylcytidines effectively inhibit the growth of molds, isolated from the paintings in the halls of the Ancient Russian Paintings of the State Tretyakov Gallery, Russia, Moscow. The novel compounds showed activity similar to antiseptics commonly used to protect works of art, such as benzalkonium chloride, to which a number of microorganisms have acquired resistance. It was also shown that the activity of N4-alkylcytidines is comparable to that of some antibiotics used in medicine to fight Gram-positive bacteria, including resistant strains of Staphylococcus aureus and Mycobacterium smegmatis. N4-dodecyl-5- and 6-methylcytidines turned out to be the best. This compound seems promising for expanding the palette of antiseptics used in painting, since quite often the destruction of painting materials is caused by joint fungi and bacteria infection. [ABSTRACT FROM AUTHOR]

In order to develop a new generation of biocides with a wide spectrum of activities suppressing both bacteria and fungi, we have synthesized a representative library of novel 3′-modified derivatives of N4-alkyl-5-methyl-2′,3′-dideoxycytidines. The replacement of the 3′-hydroxyl group with amino, aminoethyl and dialkylamino groups significantly enhances the antifungal activity, most prominently towards the Aspergillus genus. Several new compounds were able to completely inhibit the growth of all the tested moulds (at 0.7 mM) isolated from works of art at the State Tretyakov Gallery, Moscow, Russia. Thus, such compounds are promising for use as biocides for protecting works of art from mould fungi. The synthesized compounds were also assessed for bacterial growth inhibition, demonstrating MIC values slightly above those of the currently used therapeutic drugs. [ABSTRACT FROM AUTHOR]