PHYSICOCHEMICAL PROPERTIES AND ANTIMICROBIAL ACTIVITY OF NEW SPIROCYCLIC THIENO[2,3-<i>d</i>]PYRIMIDIN-4(3<i>H</i>)-ONE DERIVATIVES

Аннотация

A number of 6'-methylidene-2,3-dihydro-1H-spiro[pyridine-4,5'-thieno[2,3-d]pyrimidin]-4'(3'H)-one derivatives, obtained as major products of a domino reaction between 5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidines and electron-deficient alkynes, were characterized for their acid-base properties and lipophilicity and evaluated for the antimicrobial activity against a number of clinical isolates of bacterial and fungal strains. The cytotoxicity against four tumor cell lines was also screened for some compounds. The dissociation constants (pK_a) and partition coefficients (log P) in 1-octanol–water system were determined using a potentiometric technique. The negative difference between the observed and calculated log P values could be explained in the light of the conformational rigidity. Most of the studied compounds showed a moderate and selective activity against Gram-positive bacteria strains (S. agalactiae, E. faecalis, S. epidermidis), whereas did not exhibit any effect against Gram-negative bacteria and fungi at the maximum test concentration (500 μM). Implications of the physicochemical properties in modulating the antimicrobial activity and cytotoxicity of the examined spirocyclic thieno[2,3-d]pyrimidin-4(3H)-one derivatives are also discussed.