Isolation, characterization and biological activity of jatrophane diterpens from Euphorbia dendroides L.

Rod Euphorbia, sa više od 2.000 vrsta jednogodišnjih, dvogodišnjih ili višegodišnjih cvetnica koje su članovi familije Euphorbiaceae, jedan je od najvećih i najraznovrsnijih rodova ne samo u svojoj familiji, već u celom biljnom carstvu. Biljke ovog roda koriste se u tradicionalnoj medicini još od antičkih vremena. Dosadašnja fitohemijska proučavanja pokazala su da vrste roda Euphorbia proizvode veoma raznovrsne sekundarne metabolite, uključujući različite terpene (seskviterpeni, diterpeni i triterpeni), steroide, cerebrozide, glicerole i fenolna jedinjenja (floracetofenoni, flavonoidi, tanini, kumarini). Mnoga od ovih jedinjenja pokazuju biološke aktivnosti, a najvažnije su reverzija višestruke rezistencije na lekove, antimitotsko, antiproliferativno, citotoksično, antivirusno, antimikrobno, antitumorsko, antiinflamatorno, tumor promotorsko i proinflamatorno dejstvo. Vrste iz roda Euphorbia su bogat izvor jatrofana, makrocikličnih diterpena osnovne trans-biciklo[10.3.0]pentadekanske strukture, za koje je karakteristično postojanje veoma fleksibilnog dvanaestočlanog prstena. To su veoma funkcionalizovana, različito oksigenovana jedinjenja; u biljkama se obično nalaze u obliku polihidroksilovanih diterpena esterifikovanih različitim kiselinama (acetil, propanoil, nbutanoil, izobutanoil, izovaleril, angeloil, tigloil, benzoil, nikotinoil derivati, itd.), zbog čega su poznati i pod nazivom jatrofanski poliestri. U okviru ove disertacije ispitivani su jatrofanski diterpeni iz vrste Euphorbia dendroides L. poreklom iz Crne Gore koja do sada nije fitohemijski proučavana. Proučavanje je obuhvatalo dve celine: nadzemni deo i mlečni lateks. Iz nadzemnog dela E. dendroides izolovano je i okarakterisano šest novih jatrofana, koji su nazvani eufodendrofani A – F (1 – 5, 16), a iz mlečnog lateksa E. dendroides izolovano je i okarakterisano trinaest novih jatrofana, eufodendrofani G – S (6 – 15, 17 – 19), kao i tri jatrofana izolovana iz nadzemnih delova (1, 2, 16). Izolovani jatrofani imaju vrlo slične strukture. Jatrofani 1 – 15 se međusobno razlikuju samo po vrsti, broju i položaju supstituenata, dok se jatrofani 16 – 19 od njih razlikuju po tome što sadrže endocikličnu (Δ5) umesto egzociklične (Δ6(17)) dvostruke veze. Jedinjenja 1 – 14 su penta- ili heksaesterifikovani jatrofanski polioli koji sadrže keto grupu u položaju C-14, jednu endocikličnu 11 E– i jednu egzocikličnu C-6(17) dvostruku vezu...Genus Euphorbia, with more than 2,000 species of annual, biennial or perennial flowering plants belonging to the family Euphorbiaceae, is one of the largest and most diverse genera not only in the spurge family but in the entire plant kingdom. Plants of this genus are used in traditional medicine since ancient times. Phytochemical studies up to now have shown that the species of the genus Euphorbia produce a variety of secondary metabolites, including various terpenes (sesquiterpenes, diterpenes and triterpenes), steroids, cerebrosides, glycerols and phenolic compounds (phloracetophenones, flavonoids, tannins, coumarins). These compounds perform many different activities, including modulability of multidrug resistance, microtubuleinteracting activity, antiproliferative, cytotoxic, antiviral, antimicrobial, anticancer, antiinflammatory, tumor promoting and proinflammatory effects. Genus Euphorbia is a rich source of jatrophanes, macrocyclic diterpenes with basic trans-bicyclo[10.3.0]pentadecane structure, which are characterized by the existence of a flexible twelve membered ring. These are very functionalized compounds with various oxygenation stages; in plants are usually found in the form of polyhydroxylated diterpenes esterified with various acids (acetyl, propanoil, n-butanoyl, isobutanoyl, isovaleryl, angeloyl, tigloyl, benzoyl, nicotinoyl derivatives, etc...), and are sometimes called jatrophane polyesters. In this dissertation, jatrophane diterpenes from Euphorbia dendroides L. originating from Montenegro were investigated. The study comprises investigation of the aerial parts and of the milky latex. From the aerial parts of E. dendroides six new jatrophanes, namely euphodendrophanes A F (1 5, and 16), were isolated and characterized. From the milky latex of E. dendroides, in addition to 1, 2, and 16, the constituents of the aerial parts, thirteen new jatrophanes, euphodendrophanes G S (6 15, and 17 19), were isolated and characterized..

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

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

Antimicrobial and genotoxic activity of novel ruthenium(III) complex with n-phenyl-5-nitrosalicylideneimine

In this study, novel hexa coordinated ruthenium(III) complex of the type Na[RuCl2L2)] (where L = monobasic bidentate Schiff base derived from the condensation of 5-nitrosalicyladehyde with aniline) has been synthesized and characterized by electrospray ionization time-of-flight mass spectrometry, infrared spectroscopy and ultraviolet/visible spectrophotometry. Schiff base N-phenyl-5-nitrosalicylideneimine is coordinated to the ruthenium via imine nitrogen and phenolic oxygen. Mass spectra showed molecular ion (M-) at m/z 653.9641 which corresponds to [C26H18Cl2N4O6Ru]-. The in vitro antimicrobial properties of the Schiff base and the complex were tested by micro-dilution technique and agar plate assay for determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The compounds showed a higher antibacterial activity against tested Gram-positive bacteria (Staphylococcus aureus ATCC 33591 and ATCC 29213), whereas against the Gram-negative bacteria (Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603) were ineffective. The genotoxic effects of Ru(III) complex were investigated using the Cytokinesis Block Micronucleus (CBMN) assay in human lymphocytes cultures. The cell culture treated with the complex at a concentration of 3.7 µg/mL exhibit the most prominent effect of decreasing the frequency of micronucleus for 44%, while at the concentrations of 1.5 and 7.4 µg/mL effect is slightly lower (40%), compared to the control cell culture

Investigation of forced and total degradation products of amlodipine besylate by liquid chromatography and liquid chromatography-mass spectrometry

An isocratic, reversed-phase liquid chromatographic method was applied for the investigation of the degradation products of amlodipine besylate under the stressed conditions in solution. Amlodipine besylate stock solutions were subjected to acid and alkali hydrolysis, chemical oxidation and photodegradation as well as to the electrochemical degradation by cyclic voltammetry in 0.05 mol/L NaHCO3 on gold electrode. The total degradation of amlodipine besylate was achieved in 5 mol/L NaOH at 80°C for 6 h and the compound with molecular formula C15H16NOCl was identified as a main degradation product. Under acidic (5 mol/L HCl at 80°C for 6 h) stress conditions 75.2% of amlodipine besylate degradation was recorded. Oxidative degradation in the solution of 3% H2O2-methanol 80:20 at 80°C for 6 h showed that amlodipine besylate degraded to 80.1%. After 14 days of expose in photostability chamber amlodipine besylate solution showed degradation of 32.2%. In electrochemical degradation after 9 hours of cyclization the beginning of amlodipine oxidation was shifted for 200 mV to more negative potentials, with the degradation of 66.5%. Mass spectrometry analysis confirmed the presence of dehydro amlodipine derivate with molecular formula C20H23N2O5Cl in oxidative and acidic conditions while in electrochemical degradation was detected in traces. [Projekat Ministarsva nauke Republike Srbije, br. 172013

Hemijska analiza površinskog voska sa lišća klonova topola iz Srbije

The leaf cuticular waxes of 3 poplar clones (Populus euramericana-Pannonia (M1), and Populus deltoides PE 19/66 and B229 (Bora)) were characterized by gas chromatography-mass spectrometry method. Poplar clones grown under identical environmental conditions showed almost identical chemical content of organic compounds within analyzed leaf cuticular wax. The dominant compound was nonacosane, with range from 72,61% ± 0,02 quantified in Pannonia clone to 78,40% ± 0,35 in B229 clone, in total cuticular wax content. Other identified compounds were hexacosane, untriacontane, octacosane, tetradecanal and triacontane; the last, triacontane, was present in very small percentage in wax content, around 1% in all three clones.Površinski voskovi sa lišća od 3 klona topola (Populus euramericana cl. Pannonia (M1) i Populus deltoides cl. PE 19/66 i cl. B229 (Bora)) su analizirani metodom gasnomasene hromatografije. Klonovi topola su uzgajani pod istim uslovima spoljašnje sredine i pokazali gotovo identičan hemijski sastav u okviru analiziranog površinskog voska sa lišća. Dominantno jedinjenje je nonakozan, sa opsegom od 72,61 % ± 0,02 u klonu Pannonia do 78,40 % ± 0,35 u B229 klonu, u odnosu na ukupni hemijski sastav površinskog voska. Druga identifikovana jedinjenja su heksadekan, hentriakontan, oktadekan, tetradekanal i triakontan i poslednji, triakontan je bio prisutan u veoma malom procentu u ukupnom sadržaju površinskog voska, oko 1 % u sva tri klona

n-Alkanes in needle waxes of Picea omorika var. vukomanii

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Hemijska analiza površinskog voska sa lišća klonova topola iz Srbije

The leaf cuticular waxes of 3 poplar clones (Populus euramericana-Pannonia (M1), and Populus deltoides PE 19/66 and B229 (Bora)) were characterized by gas chromatography-mass spectrometry method. Poplar clones grown under identical environmental conditions showed almost identical chemical content of organic compounds within analyzed leaf cuticular wax. The dominant compound was nonacosane, with range from 72,61% ± 0,02 quantified in Pannonia clone to 78,40% ± 0,35 in B229 clone, in total cuticular wax content. Other identified compounds were hexacosane, untriacontane, octacosane, tetradecanal and triacontane; the last, triacontane, was present in very small percentage in wax content, around 1% in all three clones.Površinski voskovi sa lišća od 3 klona topola (Populus euramericana cl. Pannonia (M1) i Populus deltoides cl. PE 19/66 i cl. B229 (Bora)) su analizirani metodom gasnomasene hromatografije. Klonovi topola su uzgajani pod istim uslovima spoljašnje sredine i pokazali gotovo identičan hemijski sastav u okviru analiziranog površinskog voska sa lišća. Dominantno jedinjenje je nonakozan, sa opsegom od 72,61 % ± 0,02 u klonu Pannonia do 78,40 % ± 0,35 u B229 klonu, u odnosu na ukupni hemijski sastav površinskog voska. Druga identifikovana jedinjenja su heksadekan, hentriakontan, oktadekan, tetradekanal i triakontan i poslednji, triakontan je bio prisutan u veoma malom procentu u ukupnom sadržaju površinskog voska, oko 1 % u sva tri klona

Investigation of reaction between quercetin and Au(III) in acidic media: mechanism and identification of reaction products

The aim of the present paper was to investigate the reaction of quercetin, the flavonol very often used as a dietary supplement, with [AuCl4](-) ions. The reaction was studied spectrophotometrically using the equimolar solutions in 1 : 1 water-methanol at pH similar to 2. The spectrophotometric data indicated the formation of the products with an absorption maximum at 295 nm in all cases, characteristic of the oxidized forms of quercetin. HPLC coupled with DAD and LC-MS analysis of the reaction products suggested that the oxidation of quercetin resulted in the generation of similar metabolites including quinone and various oxidized quercetin-solvent adducts. In addition, cyclic voltammetric measurements confirmed that under applied experimental conditions, the reduction of Au(III) to Au(0) took place. The reduction species in the reaction mixture were Au(III) ions, while Au(I) disproportionates back to Au(III) and Au(0). The newly generated Au(III) ions further oxidized 3'-4'-dihydroxy groups of quercetin adducts obtained after first 2e(-) oxidation, giving the final reaction products. Based on the identification of reaction products, the reaction mechanism for the oxidation of quercetin in the presence of Au(III) which involves two 2e(-) transfer processes was proposed

Phenolic compounds and carotenoids in pumpkin fruit and related traditional products

Pumpkin fruit is used in a diet since ancient times especially in rural communities. The major contributory factors of nutritional and medicinal value of pumpkins are carotenoids, polysaccharides, vitamins, minerals, and phenolic compounds. Due to a very large fruit that it is not easy to consume a whole as well as short shelf-life of fresh-cut pumpkin, different ways of conserving and processing are performed. In our study, total carotenoids, total phenolics and individual phenolics in fresh pumpkin and pumpkin traditional products such as sweet in wine, jam and juice, which are typical for northern parts of Serbia, were studied. Total carotenoids ranged from 27.6 μg/g of pumpkin sweet in wine to 86.3 μg/g of fresh fruit, while the amount of total phenolics varied between 93.0 μg GAE/g of pumpkin juice and 905.9 μg GAE/g of fresh fruit. Eight phenolic compounds were identified in the investigated samples and among them phenolic acids dominated. Among flavonoids, flavanon glycoside hesperidin was detected. [Projekat Ministarstva nauke Republike Srbije, br. 46013