Umanjeno preživljavanje neoplastičkih humanih HeLa ćelija supstituisanim (E)-b-(benzoil) akrilnim kiselinama

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

Antiproliferative effects of some medicinal plants on HeLa cells

Medicinal plants maintain the health and vitality of individuals, and also have potential curative effect on various diseases, including cancer. In this study were investigated the antiproliferative effects of water extracts of previously obtained ethanolic dry extracts of three different medicinal plants (Echinacea angustifolia, Salvia officinalis and Melissa officinalis) on cell lines derived from human cervix adenocarcinoma (HeLa cells). The best cytotoxic activity (IC50 = 43.52 μg/ml) on HeLa cell lines was exhibited by Echinacea angustifolia. The extract of Salvia officinalis also showed a good cytotoxic activity against HeLa cell lines; the IC50 value was 70.41 μg/ml. Melissa officinalis manifested a slightly weaker cytotoxic activity and an IC50 value of 122.22 μg/ml. [Projekat Ministarstva nauke Republike Srbije, br. 34021 i br. 175011

Antiproliferative activity of β-hydroxy- β-arylalkanoic acids

Article describes the synthesis of fifteen β-hydroxy- β-arylalkanoic acids by Reformatsky reaction using the 1-ethoxyethyl-2- bromoalkanoates, aromatic or cycloalkyl ketones or aromatic aldehydes. The short survey of previously reported synthetic procedures for title compounds, is given. The majority of obtained compounds exert antiproliferative activity in vitro toward human: HeLa, Fem-X cells, K562, and LS174 cells, having IC 50 values from 62.20 to 205 μM. The most active compound is 3-OH-2,2-di-Me-3-(4-biphenylyl)-butanoic acid, having the IC 50 value 62.20 μM toward HeLa cells. Seven examined compounds did not affect proliferation of healthy human blood peripheral mononuclear cells (PBMC and PBMC+ PHA), IC 50 > 300 μM. The preliminary QSAR results show that estimated lipophilicity of compounds influences their antiproliferative activity in the first place. The ability of dehydration, and the spatial arrangement of hydrophobic portion, HBD and HBA in molecules are has almost equal importance as lipophilicity

Sinteza, strukturna karakterizacija i citotoksična aktivnost dva nova organorutenijum(II) kompleksa

Two new p-cymene ruthenium(II) complexes containing as additional ligands N-methylpiperazine ([(eta(6)-p-cymene)RuCl2(CH3NH(CH2)(4)NH)]PF6, complex 1) or vitamin K-3-thiosemicarbazone ([(eta(6)-p-cymene)RuCl2(K(3)tsc)], complex 2) were synthesized starting from [(eta(6)-p-cymene)(2)RuCl2](2) and the corresponding ligand. The complexes were characterized by elemental analysis, IR, electronic absorption and NMR spectroscopy. The X-ray crystal structure determination of complex 1 revealed "piano-stool" geometry. The differences in the cytotoxic activity of the two complexes are discussed in terms of the ligand present.Sintetisana su dva nova p-cimen-rutenijum(II) kompleksa koji sadrže kao dodatne ligande N-metilpiperazin ([(h6-p-cimen)RuCl2(CH3NH(CH2)4NH)]PF6, kompleks 1) i vitamin K3-tiosemikarbazon ([(h6-p-cimen)RuCl2(K3tsc)], kompleks 2). Oba nova kompleksa dobijena su polazeći od [(h6-p-cimen)2RuCl2]2 kompleksa i odgovarajućeg liganda. Kompleksi su okarakterisani elementalnom analizom, IC, elektronsko-apsorpcionom i NMR spektroskopijom. Rendgeno-strukturna analiza kompleksa 1 pokazala je “piano-stool” geometriju. U zavisnosti od prisutnog liganda diskutovana je razlika u citotoksičnoj aktivnosti ova dva dobijena kompleksa

Supplementary data for article: Pantelić, N. Đ.; Zmejkovski, B. B.; Trifunović-Macedoljan, J.; Savić, A.; Stanković, D.; Damjanović, A.; Juranic, Z.; Kaluđerović, G. N.; Sabo, T. Gold(III) Complexes with Esters of Cyclohexyl-Functionalized Ethylenediamine-N,N ’-Diacetate. Journal of Inorganic Biochemistry 2013, 128, 146–153. https://doi.org/10.1016/j.jinorgbio.2013.08.002

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2013.08.002]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1422

In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii

Background: The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Cernjavski & Soska (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC). Methods: The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. Results: The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Conclusion: Extracts obtained from the endemic plant Helichrysum zivojinii may represent an important source of novel potential antitumor agents due to their pronounced and selective cytotoxic actions towards malignant cells

Supplementary data for article: Pantelić, N. Đ.; Zmejkovski, B. B.; Trifunović-Macedoljan, J.; Savić, A.; Stanković, D.; Damjanović, A.; Juranic, Z.; Kaluđerović, G. N.; Sabo, T. Gold(III) Complexes with Esters of Cyclohexyl-Functionalized Ethylenediamine-N,N ’-Diacetate. Journal of Inorganic Biochemistry 2013, 128, 146–153. https://doi.org/10.1016/j.jinorgbio.2013.08.002

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2013.08.002]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1422

Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo

Background: Dipeptidyl peptidase IV, a multifunctional serine protease, is implicated in regulation of malignant transformation, promotion and further progression of cancer, exerting tumor-suppressing or even completely opposite - tumor-promoting activities. The aim of present research was to determine the serum DPPIV activity, as well as the percentages of CD26+ lymphocytes, CD26+ overall white blood cells and the mean fluorescence intensity of CD26 expression on lymphocytes in patients with melanoma, people with vitiligo and in healthy controls. Methods: The activity of DPPIV in serum was determined by colorimetric test. Expression of DPPIV (as CD26) on immunocompetent peripheral white blood cells was done using flow cytometry analysis. Results: Data from our study show for the first time statistically significant decrease: in the serum DPPIV activity, in the percentage of CD26+ overall white blood cells and in the percentage of lymphocytes in patients with melanoma in comparison to healthy control people. In addition, significantly lower serum DPPIV activity was found in the group of patients with melanoma in relation to people with vitiligo too. Conclusion: This study indicates the need for exploring the cause and the importance of the disturbances in the serum DPPIV activity and in the CD26 expression on immunocompetent cells in complex molecular mechanisms underlying the development and progression of melanomaThe authors are grateful to the Ministry of Education and Science of the Republic of Serbia for the financial support (Project 175011)S