<p>Cilj ove doktorske disertacije je&nbsp; bila&nbsp; sinteza novih steroidnih&nbsp;16,17-seko-16,17a-dinitrila polazeći od&nbsp;dehidroepiandrosterona (1), odnosno&nbsp; estrona (14).&nbsp; U&nbsp;androstanskoj seriji&nbsp; su izvr&scaron;ene modifikacije&nbsp; 16,17-seko-16,17a-dinitrila&nbsp; 12&nbsp; u A i/ili B prstenu steroidnog jezgra, pri&nbsp;čemu novosintetizovana jedinjenja&nbsp; sadrže&nbsp; 4-en-3-on, 1,4-dien-3-on ili 1,4,6-trien-3-on sistem, kao i supstituente u&nbsp;položajima C-4, odnosno C-6&nbsp; (6-metilen, 6-keto i 6-oksimino).&nbsp; U&nbsp; radu&nbsp; je takođe&nbsp; proučavan&nbsp; uticaj odabranih&nbsp;novosintetizovanih jedinjenja na proliferaciju sedam ćelijskih&nbsp;linija humanih tumora, dok je kao kontrola služila jedna&nbsp;zdrava humana ćelijska linija.</p> / <p>Starting from dehydroepiandrosterone (1) or estrone (14)&nbsp;new steroidal 16,17-seco-16,17a-dinitriles&nbsp; were&nbsp;synthesized. Modification of 16,17-seco-16,17a-dinitrile&nbsp;12&nbsp; afforded&nbsp; androstane derivatives containing 4-en-3-on,&nbsp;1,4-dien-3-on or 1,4,6-trien-3-on system,&nbsp; with&nbsp; different&nbsp;substituents on position C-4 or C-6 (6-methylene, 6-keto i&nbsp;6-oximino).&nbsp; Antiproliferative activity&nbsp; of&nbsp; some&nbsp; newly&nbsp;synthesized&nbsp; compounds were examined&nbsp; against&nbsp; seven&nbsp;human tumor&nbsp; cell lines,&nbsp; while healthy cells&nbsp; served as&nbsp;control.</p>

<p>U radu je ispitan uticaj odabranih modifikovanih steroida na proliferaciju ćelija humanih malignih tumora i zdravih ćelija, a zatim njihov uticaj na modifikaciju ćelijskog ciklusa, indukovanje apoptoze i genetskih o&scaron;tećenja u tumorskim ćelijama najsenzitivnijim na ova jedinjenja (MDA-MB-231 ćelijska linija humanog adenokarcinoma dojke, ER-). Ispitana je<em> in vitro </em>citotoksičnost odabranih&nbsp; steroidnih derivata prema ćelijskim linijama MCF-7, MDA-MB-231, PC3, HeLa, HT-29, MRC-5, K562 i A549, i proučavan ćelijski mehanizam koji je u osnovi uočenog antiproliferativnog efekta svakog od ispitivanih derivata. Sva ispitivana jedinjenja indukuju apoptozu MDA-MB-231&nbsp; ćelija, na različite načine i sa različitim potencijalom. Genotoksikolo&scaron;ka studija upotpunjuje rezultate proučavanja efekta ispitivanih steroidnih jedinjenja na biolo&scaron;ke sisteme, ukazujući na izostanak genotoksičnosti ovih jedinjenja i njihov biomedicinski potencijal.</p> / <p>In this work the effect of selected modified steroids on proliferation of human&nbsp; malignant tumor and healthy cells, as well as their impact on the modification of cell cycle arrest, induction of apoptosis and genetic defects in tumor cells most sensitive&nbsp; to these compounds (MDA-MB-231 cell line of human breast adenocarcinoma, ER-) were examined. We examined the<em> in vitro </em>cytotoxicity of selected steroidal derivatives towards MCF-7, MDA-MB-231, PC-3, HeLa, HT-29, MRC-5, K562 and A549 cell lines, and studied the cellular mechanism that is underlying the antiproliferative activity expressed by these steroidal derivatives. All tested compounds induced apoptosis of&nbsp; MDA-MB-231 cells, in different ways and with different potential. Genotoxicological study complements the results of the study of the effect of tested steroidal compounds on biological systems, pointing out the lack of genotoxicity of these compounds and therefore their biomedical potential.</p>

<p style="text-align: justify;">Reverzno-faznom tečnom hromatografijom pod visokim pritiskom primenom dva sistema<br />rastvarača ispitano je pona&scaron;anje i hromatografska lipofilnost prirodnih stiril laktona 7-(+)-<br />goniofufurona, 7-epi-(+)-goniofufurona, krasalaktona B i C i dvadeset njihovih<br />novosintetizovanih derivata i analoga. U ranijim ispitivanjima pokazalo se da ova jedinjenja<br />imaju veliki biolo&scaron;ki potencijal jer pokazuju zapaženu citotoksičnost prema vi&scaron;e humanih<br />tumorskih ćelijskih linija. Hromatografsko pona&scaron;anje jedinjenja uglavnom je u skladu sa<br />njihovom strukturom. Ustanovljene su linearne veze između hromatografskih retencionih<br />konstanti i većine in silico parametara lipofilnosti. Primenom hemometrijske QSRR analize<br />utvrđeni su veoma dobri multi linearni regresioni prediktivni modeli kvantitativne zavisnosti<br />između eksperimentalno dobijene hromatografske retencione konstante, koja defini&scaron;e<br />retenciju jedinjenja u čistoj vodi i in silico molekulskih deskriptora odnosno strukture<br />jedinjenja. Lipofilnost jedinjenja ima najveći uticaj na njihove farmakokinetičke, tj. ADME<br />(apsorpcija, distribucija, metabolizam, eliminacija) osobine. Definisani su i statistički<br />potvrđeni najbolji multi linearni regresioni modeli zavisnosti farmakokinetičkih parametara<br />stiril laktona i od drugih molekulskih deskriptora. In vitro citotoksična aktivnost jedinjenja<br />evaluirana je prema četiri nove humane maligne ćelijske linije: kancer prostate (PC3), kancer debelog creva (HT-29), melanom (Hs294T), adenokancer pluća (A549). Najaktivnije<br />novosintetizovano jedinjenje je triciklični 4-fluorocinamatni analog, koji ispoljava<br />nanomolarnu aktivnost (IC₅₀ 2,1 nM) prema ćelijama melanoma i aktivniji je preko 2250 puta od komercijalnog antitumorskog agensa doksorubicina (DOX). SAR analizom utvrđena je zavisnost između strukture i biolo&scaron;ke aktivnosti jedinjenja. Molekulskim dokingom ispitana je veza stiril laktona i ciljanog proteina značajnog za kancer prostate. Jedinjenja sa visokom inhibitornom aktivno&scaron;ću prema ćelijama kancera prostate imaju visok doking skor i mogu graditi koordinativno-kovalentnu vezu sa Fe²+jonom prisutnim u aktivnom centru enzima. 3D-QSAR analizom, koja je izvedena metodama komparativnih polja CoMFA i CoMSIA, formiran je značajan prediktivni model između hemijske strukture i biolo&scaron;ke aktivnosti stiril laktona.</p> / <p>The behavior and the chromatographic lipophilicity natural styryl lactone 7-(+)-<br />goniofufurone, 7-epi-(+)-goniofufurone, crassalactones B and C and twenty of their newly<br />synthesized derivatives and analogs were examined using reverse-phase high performance liquid chromatography in the two solvent systems. In previous studies it has been shown that these compounds have great biological potential toward several human tumor cell lines. Chromatographic behavior of the compounds is generally in accordance with their structure. The relationships between the chromatographic retention constants and the majority of their in silico lipophilicity parameters are linear. The application of chemometric QSRR analysis determined very good multiple linear regression predictive models of quantitative correlation between experimentally obtained chromatographic retention constant, which determines the retention of the compound in pure water and in silico molecular descriptors, i.e. the structure of the compound. The lipophilicity of the compounds has a major influence on their pharmacokinetics, i.e. ADME (absorption, distribution, metabolism, elimination) properties. The best multi-linear regression models depending on the pharmacokinetic parameters of styryl lactone and other molecular descriptors have been defined and statistically validated. In vitro cytotoxic activity of the compounds was evaluated according to four novel human malignant cell lines: prostate cancer (PC3), colon cancer (HT-29), melanoma (Hs294T), lung adenocarcinom (A549). The most active compound was tricyclic 4-fluorocinnamic analog, which exhibits a nanomolar activity (IC50 2,1 nM) toward melanoma cells. This compound is over 2250 times more active than commercial antitumor agent doxorubicin (DOX). SAR analysis has revealed a correlation between the structure and the biological activity of the compounds. Using the molecular docking the relationship of the styryl lactone and the target protein important for prostate cancer was examined. The compounds with high inhibitory activity against prostate cancer cells have a high docking score and are capable to form a coordinative-covalent bond with a Fe2+ ion present in the active centre of the enzyme. 3DQSAR analysis, which was performed by methods of comparative CoMFA and CoMSIA fields, has formed a good predictive model between chemical structure and biological activity of the styryl lactone.</p>

<p>Ispitani su hemijski sastav i biolo&scaron;ka aktivnost &scaron;est samoniklih vrsta iz tribusa Scandiceae<br />(familija Apiaceae): Anthriscus sylvestris, Anthriscus cerefolium, Chaerophyllum bulbosum,<br />Chaerophyllum hirsutum, Chaerophyllum temulentum i Scandix pecten-veneris. LC-MS-MS<br />analizom ekstrakata identifikovano je vi&scaron;e desetina sekundarnih biomolekula iz klasa flavonoida,<br />fenilpropenskih kiselina, lignana i kumarina. GC-MS analiza pružila je uvid u sastav volatilnih<br />komponenti i njihov hemosistematski značaj. Potvrđeno je da sve ispitivane vrste imaju umereno<br />antioksidantno, antiinflamatorno i antiproliferativno dejstvo.</p> / <p> Chemical composition and biological activity of six wild-growing species from<br /> Scandiceae tribe (Apiaceae family) &ndash; Anthriscus sylvestris, Anthriscus cerefolium, Chaerophyllum<br /> bulbosum, Chaerophyllum hirsutum, Chaerophyllum temulentum and Scandix pecten-veneris &ndash; was<br /> examined. By LC-MS-MS analysis, a large number of secondary biomolecules was identified in<br /> extracts, including flavonoids, phenylpropenic acids, lignans and coumarins. GC-MS analysis<br /> provided insight into volatile components composition and chemosystematic significance. All<br /> investigated species exhibited moderate antioxidant, anti-inflammatory and antiproliferative<br /> activity.</p>

<p>U ovoj doktorskoj disertaciji je radi fizičko-hemijske karakterizacije i ispitivanja potencijalne<br />biolo&scaron;ke aktivnosti sintetisano&nbsp; 40&nbsp; derivata mono(tio)karbohidrazona. Strukture dobijenih jedinjenja su potvrđene&nbsp; NMR&nbsp; i&nbsp; FT&ndash;IR&nbsp; spektroskopijom,&nbsp; elementalnom&nbsp; i&nbsp; rendgenskom&nbsp; strukturnom&nbsp; analizom. Uticaj&nbsp; rastvarača&nbsp; i&nbsp; prisutnog&nbsp; supstituenta&nbsp; na&nbsp; položaje apsorpcionih&nbsp; maksimuma&nbsp; ispitani&nbsp; su&nbsp; po principima LSER i LFER metoda. Teorijski proračuni za sintetisana jedinjenja izvedeni su&nbsp; primenom TD&ndash;DFT&nbsp; metode.&nbsp; Jonizacione&nbsp; konstante&nbsp; derivata&nbsp; mono(tio)karbohidrazona&nbsp; su&nbsp; određene potenciometrijskim&nbsp; titracijama.&nbsp; Antioksidativna&nbsp; aktivnost&nbsp; je&nbsp; određena&nbsp; primenom&nbsp; tri&nbsp; testa:&nbsp; DPPH, ABTS&nbsp; i&nbsp; FRAP&nbsp; testa.&nbsp; Antimikrobna&nbsp; aktivnost&nbsp; je&nbsp; ispitana&nbsp; mikrodilucionom&nbsp; metodom&nbsp; na&nbsp; dva&nbsp; soja bakterija:&nbsp; Staphylococcus&nbsp; aureus&nbsp; i&nbsp; Escherichia&nbsp; coli.&nbsp; Za&nbsp; jedinjenja&nbsp; koja&nbsp; su&nbsp; pokazali&nbsp; antimikrobnu aktivnost je&nbsp; ispitan procenat citotoksičnosti.&nbsp; Sveukupan&nbsp; zaključak o sličnosti i razlikama sintetisanih derivata izveden je na osnovu multivarijatnih metoda klaster analize i analize glavnih komponenti.</p> / <p>In this doctoral dissertation, 40 mono(thio)carbohydrazone derivatives were synthesized for the purpose of physico-chemical characterization and examination of potential biological activity. The structures of the obtained compounds were confirmed by NMR and FT &ndash;IR spectroscopy, elemental analysis&nbsp; and&nbsp; X-ray&nbsp; structural&nbsp; analysis.&nbsp; The&nbsp; influence&nbsp; of&nbsp; solvent&nbsp; and&nbsp; substituent&nbsp; present&nbsp; on&nbsp; the positions&nbsp; of&nbsp; absorption maxima&nbsp; was&nbsp; examined&nbsp; according&nbsp; to&nbsp; the&nbsp; principles&nbsp; of&nbsp; LSER&nbsp; and&nbsp; LFER methods.&nbsp; Theoretical&nbsp; calculations&nbsp; for&nbsp; the&nbsp; synthesized&nbsp; compounds&nbsp; were&nbsp; performed&nbsp; by&nbsp; the&nbsp; TD&ndash;DFT method.&nbsp; The&nbsp; acid&nbsp; constants&nbsp; of&nbsp; mono(thio)carbohydrazone&nbsp; derivatives&nbsp; were&nbsp; determined&nbsp; by potentiometric&nbsp; titrations.&nbsp; Antioxidant&nbsp; activity&nbsp; was&nbsp; determined&nbsp; using&nbsp; three&nbsp; tests:&nbsp; DPPH,&nbsp; ABTS&nbsp; and FRAP test. Antimicrobial activity was examined by microdilution method on two strains of bacteria: Staphylococcus&nbsp; aureus&nbsp; and&nbsp; Escherichia&nbsp; coli.&nbsp; The&nbsp; percentage&nbsp; of&nbsp; cytotoxicity&nbsp; was&nbsp; examined&nbsp; for compounds&nbsp; that&nbsp; showed&nbsp; antimicrobial&nbsp; activity.&nbsp; Overall&nbsp; conclusion&nbsp; about&nbsp; the&nbsp; similarities&nbsp; and differences of the synthesized&nbsp; derivatives was studied by multivariate&nbsp; methods of cluster analysis and analysis of principal components.</p>

<p>U ovoj doktorskoj disertaciji ispitan je hemijski sastav i biolo&scaron;ke aktivnosti<br />ekstrakata deset&nbsp; samoniklih&nbsp; taksona roda&nbsp; <em>Allium</em>&nbsp; sect.&nbsp;<em> Codonoprasum:&nbsp; A. carinatum</em>&nbsp;subsp. <em>pulchellum,&nbsp; A. carinatum&nbsp;</em> subsp. <em>carinatum,&nbsp; A. fuscum&nbsp;</em> var. <em>gracile,&nbsp; A. fuscum&nbsp;</em> var.&nbsp;<em>fuscum,&nbsp; A. flavum</em> subsp. <em>flavum,&nbsp; A. melanantherum,&nbsp; A. paniculatum&nbsp;</em> subsp.&nbsp;<em> marginatum,&nbsp;A. pallens</em>&nbsp; subsp. <em>tenuiflorum,&nbsp; A. oleraceum&nbsp; </em>i&nbsp;<em> A. rhodopeum</em>, sakupljenih na&nbsp; 27 lokaliteta&nbsp;u Srbiji. Cilj rada bio je da se dobiju podaci o sadržaju biolo&scaron;ki aktivnih jedinjenja u&nbsp;ovim, do sada veoma malo ispitanim vrstama roda&nbsp; <em>Allium</em>, i utvrdi njihova potencijalna&nbsp;lekovita vrednost.</p><p>Analiza hemijskog sastava obuhvatila je: analizu volatilnih komponenti svežih&nbsp;<br />lukovica primenom headspace GC-MS tehnike, kvalitativnu analizu metanolnih &nbsp;<br />ekstrakata primenom tečnohromatografskih metoda (LC-DAD-MS i LC-MS-MS), &nbsp;<br />kvantitativnu analizu odabranih fenolnih jedinjenja LC-MS-MS tehnikom,&nbsp; određivanje&nbsp;sadržaja ukupnih&nbsp; monomernih&nbsp; antocijana&nbsp; i određivanje aktivnosti aliinaze. Ispitivanja&nbsp;biolo&scaron;kih aktivnosti ekstrakata obuhvatila su: određivanje antioksidantne,&nbsp;antiinflamatorne, antimikrobne, antimutagene i genotoksične aktivnosti, kao i ispitivanje&nbsp;uticaja na rast zdravih i tumorskih ćelija i sposobnosti indukcije ćelijske smrti.&nbsp;</p><p>Sumiranjem dobijenih rezultata može se zaključiti da ispitivani predstavnici roda&nbsp;<br /><em>Allium&nbsp;</em> sect.&nbsp; <em>Codonoprasum&nbsp;</em> predstavljaju bogate izvore biolo&scaron;ki aktivnih jedinjenja sa&nbsp;&scaron;irokim spektrom biolo&scaron;kih aktivnosti. Sa hemotaksonomskog aspekta značajno je da se&nbsp;dimetil-disulfid&nbsp; izdvaja kao&nbsp; najdominantnija&nbsp; i često jedina&nbsp; isparljiva komponenta, da&nbsp;ekstrakti većine vrsta&nbsp; sadrže veliku količinu flavonoida (prvenstveno derivata&nbsp;kvercetina), da se vrste&nbsp;<em> A. pallens&nbsp;</em> i&nbsp; <em>A. oleraceum</em>&nbsp; izdvajaju od ostalih po tome &scaron;to ne&nbsp;sadrže rutin&nbsp; a sadrže&nbsp; hiperozid,&nbsp; da je vrsta&nbsp;<em> A. rhodopeum</em>&nbsp; siroma&scaron;na fenolnim&nbsp;jedinjenjima i da su sve vrste, osim vrste&nbsp; <em>A.&nbsp; flavum</em>, bogate antocijanima. Aktivnost&nbsp;aliinaze je visoka u svim ispitivanim vrstama. Većina ispitivanih ekstrakata, izuzev&nbsp;ekstrakata vrsta&nbsp; <em>A. carinatum&nbsp;</em>i <em>A. melanantherum</em>, pokazala je izraženu antioksidantnu&nbsp;aktivnost, dok su ekstrakti vrsta <em>A. flavum</em>, <em>A. rhodopeum</em>, <em>A. oleraceum </em>i <em>A. paniculatum&nbsp;</em>snažni antiinflamatorni agensi. Ekstrakti ispitivanih predstavnika sect.&nbsp;<em> Codonoprasum&nbsp;</em>nisu pokazali antimikrobnu i antimutagenu aktivnost. Takođe, ovi ekstrakti nisu ispoljili&nbsp;genotoksični efekat na ćelije zdravog tkiva (izuzev slabog genotoksičnog efekta ekstrakta&nbsp;nadzemnih delova&nbsp;<em> A. flavum</em>), &scaron;to ukazuje na bezbednost upotrebe vrsta sect.&nbsp;<em>Codonoprasum&nbsp;</em> kao hrane ili u obliku lekova. Ekstrakti celih biljaka&nbsp;<em>A. paniculatum</em> i <em>A.&nbsp;rhodopeum</em>, kao i ekstrakt nadzemnih delova &nbsp;<em>A. melanantherum</em>&nbsp; pokazali su snažnu&nbsp;antiproliferativnu aktivnost sa povoljnim ne-tumor/tumor koeficijentima i indukovali&nbsp;apoptozu u tumorskim ćelijama, iz čega se može zaključiti da imaju visok potencijal&nbsp;primene u antitumorskoj terapiji.&nbsp;</p> / <p>In the present doctoral thesis the chemical composition and biological activities&nbsp; of&nbsp;<br />10 wild growing taxa of genus&nbsp; <em>Allium</em>&nbsp; sect. <em>Codonoprasum</em>&nbsp; (<em>A. carinatum&nbsp;</em> subsp.&nbsp;<br /><em>pulchellum,&nbsp; A. carinatum&nbsp;</em> subsp.&nbsp; <em>carinatum,&nbsp; A. fuscum&nbsp;</em> var.&nbsp; <em>gracile,&nbsp; A. fuscum</em>&nbsp; var.&nbsp;<br /><em>fuscum,&nbsp; A. flavum&nbsp;</em> subsp.&nbsp; <em>flavum,&nbsp; A. melanantherum,&nbsp; A. oleraceum,&nbsp; A. paniculatum</em><br />subsp. <em>marginatum, A. pallens</em> subsp. <em>tenuiflorum</em> and <em>A. rhodopeum</em>) were investigated.&nbsp;The samples were&nbsp; collected from 27 locations in Serbia. The aim of the study was to&nbsp;obtain data on the content of biologically active compounds in extracts of &nbsp;these&nbsp;unexplored species of the genus Allium and to determine their potential medicinal value.</p><p>Phytochemical caracterisation included: headspace GC-MS analysis of fresh bulb&nbsp;<br />volatiles, LC-DAD-MS and LC-MS-MS qualitative analysis of methanol extracts, LC-MS-MS quantitative analysis of 44 selected phenolic compounds in methanol extracts,&nbsp;determination of total monomeric anthocyanins content and alliinase activity. In order to&nbsp;assess the biological potential of methanol extracts, the antioxidant, anti-inflammatory,&nbsp;antimicrobial, antimutagenic, genotoxic and antiproliferative activities of &nbsp;the extracts&nbsp;were studied.</p><p>Summing up all the results obtained, it can be concluded that species of genus&nbsp;<em>Allium&nbsp;</em> sect.&nbsp; <em>Codonoprasum&nbsp;</em> are rich sources of biologically active compounds with a&nbsp;broad spectrum of biological activities. Dimethyl disulfide is the most dominant and&nbsp;often the only volatile component of most species, which is significant from&nbsp;chemotaxonomic point of view. The methanol extracts of investigated species contain&nbsp;high levels of flavonoids (primarily quercetin derivatives). Specificity of&nbsp; <em>A. pallens</em>&nbsp; and&nbsp;<em>A. &nbsp;oleraceum</em>&nbsp; extracts is that they do not contain rutin, but contain hyperoside, while&nbsp;small quantity of phenolic compounds&nbsp; is characteristic for&nbsp; <em>A. rhodopeum</em>&nbsp; extract. All&nbsp;investigated species, except of <em>A. flavum</em>, are rich in anthocyanins. Alliinase activity was&nbsp;high in&nbsp; all examined species. Most of the extracts, except&nbsp; <em>A. carinatum</em>&nbsp; and&nbsp; <em>A.&nbsp;melanantherum</em>&nbsp; extracts, express considerable antioxidant activity, &nbsp;while extracts of&nbsp;<em> A.&nbsp;flavum</em>,&nbsp; <em>A. rhodopeum</em>,&nbsp; <em>A. paniculatum</em>&nbsp; and&nbsp; <em>A. oleraceum&nbsp;</em> are potent anti-inflammatory&nbsp;agents. The investigated&nbsp; <em>Allium</em>&nbsp; extracts did not show antimicrobial and antimutagenic&nbsp;activity. Also, the extracts did not express genotoxic effect on healthy tissue cells&nbsp;(except the weak genotoxic effects of aerial parts extract of&nbsp; <em>A. flavum</em>), indicating that&nbsp;the use&nbsp; of these species as a food or as a drug is safe. Whole plant extracts of&nbsp; <em>A.&nbsp;paniculatum</em>&nbsp; and&nbsp;<em> A. rhodopeum</em>, as well as aerial parts extract of&nbsp;<em> A. melanantherum</em>&nbsp;showed strong antiproliferative activity (with a favorable &nbsp;non-tumor/tumor ratios) and&nbsp;induced apoptosis in tumor cells, suggesting that these plants have a high potential for&nbsp;application in antitumor therapy.</p>

<p>U ovom radu su ispitani hemijski sastav i biolo&scaron;ka aktivnost vrsta&nbsp;<em> Brassica oleracea&nbsp; </em>i<em>&nbsp; Brassica rapa</em>&nbsp; poreklom iz organskog i konvencionalnog sistema proizvodnje. Ispitivanja hemijskog sastava su obuhvatila određivanje volatilnih komponenata primenom headspace GC-MS tehnike, kvalitativnu analizu sokova ispitivanih vrsta pomoću LC-DAD-MS/MS tehnike, kvantifikaciju odabranih fenolnih jedinjenja&nbsp;pomoću LC-MS/MS tehnike i spektrofotometrijsko određivanje sadržaja ukupnih glukozinolata, fenola i flavonoida i sadržaja ukupnih monomernih antocijana. Biolo&scaron;ka aktivnost povrća je ispitana određivanjem antioksidantnog potencijal, antimikrobne i antitumorske aktivnosti sokova. Dobijeni rezultati pokazuju da su glavne volatilne komponente ispitivanih vrsta degradacioni proizvodi masnih kiselina i organosumpornih jedinjenja od kojih neke od identifikovanih komponenata predstavljaju ključne mirisne komponente. Na osnovu njihove distribucije nije bilo moguće utvrditi uticaj sistema proizvodnje na miris i ukus ispitivanih vrsta. Pomoću LC-DAD-MS/MS i LC-MS/MS tehnike je utvrđeno prisustvo primarnih metabolita, slobodnih hidroksibenzoevih i hidroksicimetnih kiselina, derivate hinske kiseline&nbsp;sa hidroksicimetnim kiselinama, glikozida flavonola, biflavonoida, i kumarina u sokovima spitivanih vrsta. Pored toga u svim sokovima subili prisutni kondenzacioni proizvodi degradacionih proizvoda indolnih glukozinolata sa askorbinskom kiselinom-&nbsp; askorbigen i metoksiaskorbigen. U sokovima crvenog kupusa su bili prisutni antocijani. Najveći sadržaj ukupnih glukozinolata je određen u brokoliju, dok je crveni kupus sadržao najveći sadržaj ukupnih fenola ukupnih flavonoida kao i hinske kiseline. Crveni kupus je bio varijetet koji je ispoljio najvi&scaron;i antioksidantni kapacitet u svim primenjenim testovima, brokoli i karfiol su ispoljili najjaču antimikrobnu aktivnost, dok je kelj bio varijetet sa najjačim antitumorskim delovanjem. Na osnovu analize hemijskog sastava i biolo&scaron;ke aktivnosti vrsta <em>B</em>. <span id="cke_bm_177S" style="display: none;">&nbsp;</span><em>oleracea</em><span id="cke_bm_177E" style="display: none;">&nbsp;</span> i&nbsp;<em> B. rapa</em>&nbsp; može se <span id="cke_bm_178E" style="display: none;">&nbsp;</span>zaključiti da u zavisnosti od primenjenog tipa&nbsp;proizvodnje mogu biti pobolj&scaron;ane neke od karakteristika ispitivanih vrsta i da je uticaj sistema proizvodnje značajan za pojedine varijetete, a nikako za celu vrstu. U konačnom obliku može se zaključiti da bi potencijalna kombinacija sokova crvenog kupusa, brokolija, karfiola i kelja mogla ostvariti značajno hemopreventivno i hemoterapeutsko delovanje, ispoljavajući istovremeno antioksidantnu, antimikrobnu i antitumorsku aktivnost.</p> / <p>Chemical composition and biological activity of<em>&nbsp; Brassica oleracea</em>&nbsp; and&nbsp; <em>B. rapa&nbsp;</em> species were investigated in the present work. Investigation of chemical composition&nbsp; encompassed determination of volatile compounds by headspace GC-MS technique, qualitative analysis of juices of investigated vegetables by LC-DAD-MS/MS technique, quantification of selected phenolic compounds by LC-MS/MS technique and spectrophotometric determination of total content of glucosinolates, phenolic compounds and flavonoids and total content of monomeric anthocyanes. Biological activity of vegetables was investigated by determination of antioxidant capacity, antimicrobial and antitumorigenic effect of juices. Obtained results showed that main volatile compounds were degradation products of fatty acids and organo-sulphur compounds among which some of the identified components were the key aroma compounds. Based on their distribution it was not possible to evaluate influence of cropping system on aroma and taste of investigated species. By LC-DAD-MS/MS and LC-MS/MS techniques, it was determined the presence of primary metabolites, freehydroxybenzoic and hydroxycinnamic acids, derivatives of quinic acid and hidroxicinnamic acids, flavonol glucosides, biflavnoids&nbsp; and a cumarin in juices of the investigated species. Furthermore, condensation products of degradation products of indole glucosinolates with ascorbic acid-&nbsp; ascorbigen and metoxiascorbigen were present in all juices. Anthocyanes were present in juices of red cabbage. The highest total content of glucosinolates was determined in broccoli, while red cabbage had the highest total phenolic content, total flavonoid content, as well as content of qunic acid. Red cabbage was a variety that showed the highest antioxidant capacity measured by different assays. Broccoli and cauliflower expressed the highest antimicrobial potential, while Savoy cabbage was a variety with the highest antitumor effect. Investigation of chemical composition and biological activity showed that applied cropping conditions may be useful for improving some of the characteristics of investigated species and significance of cropping system only&nbsp; for particular varieties, but not for the whole species in general. As the conclusion, potential&nbsp; combination of juices of red cabbage, broccoli, cauliflower and Savoy cabbage could be potent chemopreventive and chemotherapeutic agent, expressing simultaneously antioxidant, antimicrobial and antitumor activity.</p>

<p>U ovoj doktorskoj disertaciji ispitane su 1,3-dipolarne<br />cikloadicione reakcije steroidnih azido-nitrila, nitrona i<br />nitril-oksida, pri čemu su sintetizovana različita<br />heterociklična steroidna jedinjenja androstanske i estranske<br />serije. Utvrdjene su strukture novosintetizovanih<br />jedinjenja. Ispitana je biolo&scaron;ka aktivnost odabranih<br />jedinjenja.</p> / <p>In this PhD thesis 1,3-dipolar cycloadditions of<br />steroidal azido-nitriles, nitrones and nitrile-oxide were<br />examined. Various steroidal heterocyclic compounds in<br />the androstane and estrane series were synthesised. The<br />structural characterisation of newly synthesised<br />compounds was done. Biological activity of selected<br />compounds was examined.</p>