Sekundarni metaboliti biljne vrste Hypericum monogynum iz Pakistana

4-Chlorobenzoic acid (1), quercitrin (2), astilbin (3), along with beta-sitosterol, gamma-sitosterol, friedelin and beta-amyrin were isolated from the aerial parts of Hypericum monogynum. Whereas compound 1 was isolated for the first time from natural sources, flavanonol 3 was not found before in these species.4-Hlorobenzoeva kiselina (1), kvercitrin (2), astilbin (3), kao i β-sitosterol, γ- sitosterol, fridelin i β-amirin izolovani su iz nadzemnih delova biljne vrste Hypericum monogynum. Po prvi put jedinjenje 1 je izolovano iz prirodnih izvora, dok flavanonol 3 do sada nije izolovan iz ove biljne vrste

Reaction of Cross-Conjugated Systems With Diisobutylaluminium-Hydride and Oxygen

After discovering that conjugated ketones may be converted to syn-epoxy-alcohols by DIBAH and oxygen, the investigation was expanded to cross-conjugated dienone systems, i. e. «-santonln and adrosta-1,4-diene-3,17-dione. The addition of 1 M DIBAH in toluene converted these dienones to intermediate aluminoxy derivatives which, after passing oxygen through the reaction mixture and continuous addition of DIBAH, gave the corresponding syn-epoxy-alcohols. No formation of diepoxy and anti-epoxy-alcohols was observed

Konformaciona analiza tri germakranolida PM3 semi-empirijskom metodom

The conformations of the C-6 lactomized germacranolides 1-3 were calculated by applying the PM3 semi-empirical method, The low-temperature H-1-NMR spectra of parthenolide (1) were also measured. The relations between the calculated and the experimentally determined geometries were established using a modified Karplus equation. The applied quantum-chemical calculations proved to be an efficient and easy-to-use tool for die elucidation and prediction of die properties of germacranolide-type sesquiterpene lactones.Konformacije germakranolida 1–3, laktonizovanih u položaju (6), izračunate su primenom PM3 semi-empirijske MO metode. Takođe su snimljeni protonski NMR spektri partenolida (1) na niskim temperaturama. Pomoću modifikovane Karplusove jednačine je uspostavljena korelacija između eksperimentalno utvrđenih i izračunatih najstabilnijih konformacija. Zaključeno je da primenjena kvantno-hemijska izračunavanja brzo i pouzdano mogu predvideti i objasniti osobine seskviterpenskih laktona tipa germakranolida

Supplementary material for the article: Krstić, G.; Jadranin, M.; Todorović, N. M.; Pešić, M.; Stanković, T.; Aljančić, I. S.; Tešević, V. V. Jatrophane Diterpenoids with Multidrug-Resistance Modulating Activity from the Latex of Euphorbia Nicaeensis. Phytochemistry 2018, 148, 104–112. https://doi.org/10.1016/j.phytochem.2018.01.016

Supplementary material for: [https://doi.org/10.1016/j.phytochem.2018.01.016]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2108

Два нова јатрофанска дитерпена из корена Euphorbia nicaeensis

In the previous study fifteen jatrophane diterpenes were isolated from the Euphorbia nicaeensis latex. Fourteen of them have been shown to be potent P-glycoprotein (P-gp) inhibitor in two MDR cancer cells (NCI-H460/R and DLD1-TxR). The aim of this study was to determine whether and which jatro­phane diterpenes can be isolated from the root of the plant, and then to examine their inhibition power on P-glycoprotein of selected cancer cell lines (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR and U87-TxR). Two previously undes­cribed jatrophane diterpenes were isolated from the root of E. nicaeensis col­lected in Deliblato Sand (Serbia). The structures of the isolated compounds were determined using 1D and 2D NMR, as well as HRESIMS data. The results obtained by MTT assay showed different antitumor potential of these two jatrophanes. Compound 1 inhibited cell growth of non-small cell lung car­cinoma cell lines NCI-H460 and NCI-H460/R, as well as glioblastoma cell lines U87 and U87-TxR, while jatrophane 2 was almost completely inactive in the suppression of cancer cell growth in a given range of concentrations. The obtained results also showed that the isolated compounds have an inhibitory effect on P-glycoprotein, as well as that their inhibitory potential is similar.У претходном истраживању, петнаест дитерпена јатрофанског типа изоловано је из латекса Euphorbia nicaeensis. Њих четрнаест показала су се као снажни инхибитори P-гликопротеина (P-gp) у две MDR ћелијске линије рака (NCI-H460/R и DLD1-TxR). Циљ ове студије био је да се утврди да ли је и које јатрофанске дитерпене могуће изо- ловати из корена биљке, а затим испитивање њихове инхибиторне моћи на P-гликопро- теину одабраних ћелијских линија рака (NCI-H460, DLD1, U87, NCI-H460/R, DLD1-TxR и U87-TxR). Два претходно непозната јатрофана изолованa су из корена E. nicaeensis прикупљеног у Делиблатској пешчари. Структуре изолованих једињења одређене су применом 1D и 2D NMR метода, као и HRESIMS експеримента. Резултати добијени МТТ тестом показали су различит антиканцерогени потенцијал ова два јатрофана. Једињење 1 је инхибирало раст ћелија ћелијских линија неситноћелијског карцинома плућа NCI-H460 и NCI-H460/R, као и ћелијских линија глиобластома U87 и U87-TxR, док је јатрофан 2 био готово потпуно неефикасан у сузбијању растa ћелија карцинома у датом концентрационом опсегу. Добијени резултати су такође показали да 1 и 2 имају инхибиторно дејство на P-гликопротеин, као и да је њихов инхибиторни потенцијал сличан.Part of the theme issue honoring Professor Emeritus Slobodan Milosavljevićs 80th birthday

Supplementary material for the article: Krstić, G.; Jadranin, M.; Todorović, N. M.; Pešić, M.; Stanković, T.; Aljančić, I. S.; Tešević, V. V. Jatrophane Diterpenoids with Multidrug-Resistance Modulating Activity from the Latex of Euphorbia Nicaeensis. Phytochemistry 2018, 148, 104–112. https://doi.org/10.1016/j.phytochem.2018.01.016

Supplementary material for: [https://doi.org/10.1016/j.phytochem.2018.01.016]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2108

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

Jatrophane Diterpenoids With Protective Effect on Human Lymphocytes DNA

Two sets of structurally different jatrophanes (1-11 and 13-16), jatrophane 12, and latex extract of 2 Euphorbia species (17 and 18) were tested for in vitro protective effect against chromosome aberrations in peripheral human lymphocytes using the cytokinesis-block micronucleus (CBMN) assay. Jatrophanes 1-6 in minimal doses of 1 µg/mL prominently decreased micronuclei (MN) frequency in the range 44.86% to 34.29% and manifested considerable protective effect. From the other set of jatrophanes, 13 in the same minimal dose notably decreased MN frequency by 31.05%, while extracts 17 and 18 at a concentration of 4 µg/mL remarkably decreased the frequency of MN by 37.94% and 36.12%, respectively. Jatrophanes 12, 14, and 16 showed moderate protection, while 7-11 and 15 were less active than positive control. The structure-activity relationship (SAR) studies of the tested jatrophanes (1-16) indicated the favorable position of benzoate at C-8 or C-9 (3, 4, and 13) and a preference of isobutanoyloxy group at C-3 (1-3) rather than propanoyloxy at the same position (4-6) for pronounced protective effect on human lymphocytes DNA. In a previous SAR study on 11 jatrophanes (1, 3-8, and 13-16), the same structural features in 3, 4, and 13 influenced powerful inhibition of P-gp, while growth inhibition of cancer cells was more than doubled in 1 (isobutanoyloxy group at C-3) compared to 6 (propanoyloxy at C-3)

Leaf epicuticular waxes of eleven Euphorbia species (Euphorbiaceae) from the central Balkans: Impact on chemotaxonomy

The presence of n-alkanes, free alcohols and free acids in leaf epicuticular wax extracts of 22 samples of 11 Euphorbia L. species belonging to the sections Paralias, Esula, Myrsiniteae and Helioscopia, 10 of which were never examined before, were analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS), and n-alkane C27 was detected as the principal component of leaf epicuticular waxes in the majority of the examined species, while the most abundant free alcohol was C26. Three Euphorbia species belonging to section Helioscopia were characterized by a predominance of alcohol C28. Free acid (C16) was the major component in 21 investigated samples. The usefulness of n-alkanes and free alcohols and free acids as potential chemotaxonomic markers is briefly discussed

Development and validation of an LC-MS/MS method with a multiple reactions monitoring mode for the quantification of vanillin and syringaldehyde in plum brandies

An ultra-performance liquid chromatographic triple quadrupole mass spectrometric (UPLC-QqQ-MS/MS) method with a multiple reactions monitoring mode (MRM) was developed and validated for the quantification of vanillin and syringaldehyde in plum brandy. The method showed good linearity (0.05 to 10 mg L-1) and low limits of detection and quantification (the LOD and LOQ values were 11.6 and 38.2 mu g L-1 for vanillin, and 12.7 and 42.0 mu g L-1 for syringaldehyde, respectively). The overall intra-day and inter-day variations were less than 4.21 % and the overall recovery was over 93.0 %. The correlation coefficients (R-2) of the calibration curves were higher than 0.9999. In order to evaluate whether the method was suitable for use as a routine analytical tool, vanillin and syringaldehyde were determined in 31 samples of Serbian plum brandy