Journal of the Serbian Chemical Society (Sep 1999)
Substitued (E)-b-(benzoyl)acrylic acids suppressed survival of neoplastic human HeLa cells
Abstract
The bacteriostatic activity of some of alkyl substituted (E)-b-(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)-b-(benzoyl)acrylic acids, against human cervix carcinoma, HeLa, cells. Target HeLa cells were continuously treated with increasing concentrations of substituted (E)-b-(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)-b-(benzoyl) acrylic acid leads to the expression of cytostatic activity against HeLa cells (IC50 were in the range from 31-40 µM). Their antiproliferative action was less than that of the basic compound (E)-b-(benzoyl)acrylic acid whose IC50 was 28.5 µM. The 3,4-dimethyl-, 2,4-dimethyl- and 2,5-dimethyl- derivatives as well as the 4-ethyl- and 3,4-dichloro- and 2,4-dichloro-derivatives, have stronger cytostatic activity than the correspoding monosubstituted and parent compound. Their IC50 were 18.5 µM; 17.5 µM; 17.0 mM; 17.5 µM; 22.0 µM and 18 µM, 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 µM and 6.5 µM 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 µM and 5.5 µM, respectively. The investigated compounds affected the survival of HeLa cells, expressing a strong structure-activity relationship of the Hansch type.
