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 μM). Their antiproliferative action was less than that of the basic compound (E)-β-(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 μM; 17.5 μM; 22.0 μM and 18 μM, respectively. The 4-iso-propyl-and 4-n-butyl-derivatives excited 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.

Još ranije je pokazana bakteriostatska aktivnost nekih alkil supstituisanih (E)-b-(benzoil)akrilnih kiselina. Cilj ovog rada je bio proučavanje antiproliferativnog dejstva 19 (E)-b-(benzoil)akrilnih kiselina, alkil-, ili halogeno-, ili metoksi-, ili acetamido-supstituisnaih, na ćelije humnog karcinoma grlića materice, HeLa ćelije. Ciljne HeLa ćelije, su kontinualno tretirane rastućim koncentracijama supstituisanih (E)-b-(benzoil)akrilnih kiselina tokom dva dana. MTT test je korišćen za utvrđanje antiproliferativnog dejstva ovog jedinjenja. Tretiranje HeLa ćelija 4-metil-, 4-fluoro, 4-hloro-, 4-bromo- i 4-metoksi-derivatima (E)-b-(benzoil)akrilne kiseline dovelo je do ispoljavanja citostatske aktivnosti prema HeLa ćelijama (IC50 su između 31.40 mM). Njihovo antiproliferativno dejstvo je bilo manje nego kod osnovnog jedinjenja, (E)-b-(benzoil)akrilne kiseline, čije IC50 je bilo 28,5 mM. 3,4-Dimetil-, 2,4-dimetil- i 2,5-dimetil- supstituisani, kao i 4-etil- te 3,4-dihloro-i 2,4- dihloro- derivati, imaju jaču citostatsku aktivnost od odgovarajućeg monosupstituisanog i osnovnog jedinjenja.Njihove IC50 vrednosti su 18,5 mM; 17,5 mM, 17,0 mM; 17,5 mM; 22,0 mMi18mM, u navedenom redosledu. 4-iso-Propil- i 4-n-butil-derivati pokazuju višu citostatsku aktivnost od jedinjenja sa manjim brojem metilenskih –CH2. grupa u supstituentu. Wihove IC50 vrednosti su 14,5 mM odnosno 6,5 mM. 2,5-Di-iso-propil- i 4-tert-butil- derivati ispoqavaju najjače antiproliferativno dejstvo prema ispitivanim HeLa ćelijama, IC50 su 4,5 mM i 5,5 mM u navedenom redosledu. Proučavana jedinjenja utiču na pre.ivqavawe HeLa ćelija, ispoljavajunji izrazitu relaciju Hanschovog tipa između strukture i biološke aktivnosti.