Abstract

SYNTHESIS, STRUCTURAL AND SPECTRAL ANALYSIS OF SOME 8- SUBSTITUTED DERIVATIVES OF 1,3,7-TRIMETHYLXANTHINE WITH ANTIPROLIPHERATIVE ACTIVITY

Maya Georgieva*, Javor Mitkov , Georgi Momekov, Branimir Zlatkov, PlamenPeikov, Alexander Zlatkov

ABSTRACT

The synthesis of methylxanthine derivatives could be a good approach to develop new analogues with similar or novel pharmacological profiles including antiproliferative activity. The synthesis of four derivatives of 1,3,7-trimethylxanthine with substituents containing allantoin and saccharine in the side chain on 8th position in the xanthine ring was studied. The theoretical structure of the investigated compounds was compared to the crystallographic data for caffeine, allantoin and saccharin and a good agreement between theoretical and experimental data was established. The results from FTIR, 1H-NMR and 13C-NMR spectral analysis confirmed the proposed structures of the tested compounds. The theoretical UV spectra correspond to the experimentally observed. It was proven that in compounds 6a,b, the 2,5-dioxo-4-ureidoimidazolidine is bound to the alkyl side chain at position 1, and not at position 3. The estimated redox potential for all compounds is about 8.31–8.73 eV. According to the corresponding calculated HOMO and LUMO values the analyzed structures may be considered as reductors. The presented Nsubstituted 8-aminocaffeine derivatives exhibit antiproliferative effects on human tumor cell lines of different origin and cellular type and could be subset to further modification aimed at identifying prospective antineoplastic lead compounds.

Keywords: substituted 8-aminocaffeines, structural analysis, spectral analysis, antiprolipherative activity.