The bacteriostatic activity of some of alkyl substituted
(E)-?-(benzoyl)acrylic acids was shown earlier. The aim of this study was to
investigate the antiproliferative action of 19 alkyl-, or halogeno-, or
methoxy-, or acetamido-substituted (E)-?-(benzoyl)acrylic acids, against
human cervix carcinoma, HeLa, cells. Target HeLa cells were continuously
treated with increasing concentrations of substituted (E)-?-(benzoyl)acrylic acids during two days. The MTT test was used for assessment of
the antiproliferative action of this group of compounds. Treatment of HeLa
cells with 4-methyl-, 4-fluoro-, 4-chloro-, 4-bromo- and 4-methoxy-
derivatives of (E)-?-(benzoyl) acrylic acid leads to the expression of
cytostatic activity against HeLa cells (IC50 were in the range from 31.40
mM). Their antiproliferative action was less than that of the basic compound
(E)-?-(benzoyl)acrylic acid whose IC50 was 28.5 mM. The 3,4-di-methyl-,
2,4-dimethyl- and 2,5-dimethyl-derivatives as well as the 4-ethyl- and
3,4-di-chloro- and 2,4-dichloro-derivatives, have stronger cytostatic
activity than the correspoding monosubstituted and parent compound. Their
IC50 were 18.5 mM; 17.5 mM; 17.0 mM; 17.5 mM; 22.0 mMand 18 mM,
respectively. The 4-iso-propyl- and 4-n-butyl- derivatives exerted higher
cytostatic activity than the compounds with a lower number of methylene
-CH2. groups in the substitutent. Their IC50 were 14.5 mM and 6.5 mM
respectively. The 2,5-di-iso-propyl- and 4-tert-butyl-derivatives expressed
the most strong antiproliferative action against the investigated HeLa
cells, IC50 being 4.5 mM and 5.5 mM, respectively. The investigated
compounds affected the survival of HeLa cells, expressing a strong
structure-activity relationship of the Hansch type.
The protolytic equilibria of 13 4-aryl-2,4-dioxobutanoic acids (ADKs) were spectrophotometrically studied in aqueous solutions in the pH range 1-9 at 25??1??C and an ionic strength of 0.1 mol l (NaCl), with the exception of the 4-OH-derivative which was also potentiometrically studied in the pH range 7-10 at 25??1??C and an ionic strength of 0.1 mol l (NaCl). In solution, the compounds simultaneously exist in one diketo and two enolic forms; therefore, the determined acidity constants (pZ 1.87-2.29, pK 6.63-8.13 and pK(4-OH-) 9.52) represent system macro constants. The H-NMR spectrum of the parent compound (4-phenyl-2,4-dioxobutanoic acid) (25??C, pD 5.0) proved the existence of all tautomeric forms. Using the extended Hammett relation, the determined pK values were correlated with literature ?? values. The predicted pK values were in fair accordance with the experimentally observed ones. Molecular, monoanionic and dianionic forms of the parent compound were optimized by the semi-empirical molecular orbital PM6 method using the implicit water solvation model (COSMO). The obtained geometries were used to explain the quality of the LFER models
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