Substitued (E)-β-(benzoyl)acrylic acids suppressed survival of neoplastic human hela cells

Abstract

The bacteriostatic activity of some of alkyl substituted (E)-β-(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)-β-(benzoyl)acrylic acids, against human cervix carcinoma, HeLa, cells. Target HeLa cells were continuously treated with increasing concentrations of substituted (E)-β-(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)-β-(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)-β-(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.

Keywords

• benzoylacrylic acids
• hela cells
• cytotoxicity
• qsar