Objectives
The chemical composition, antimicrobial and synergistic effect, and cytotoxic activity of Citrus limon (lemon), Piper nigrum (green pepper) and Melaleuca alternifoila (tea tree) essential ...oils (EOs) were investigated.
Methods
Chemical analyses of essential oils were tested by GC‐FID and GC‐MS spectroscopy. The antimicrobial activity assay was conducted using microdilution method against several oral bacteria and Candida spp. originating from the humans with oral disorders. The synergistic antimicrobial activity was evaluated using checkerboard method. The cytotoxicity evaluation of EOs was assessed using MTT test.
Key findings
Limonene (37.5%) and β‐pinene (17.9%) were the major compounds in C. limon oil, β‐pinene (34.4%), δ‐3‐carene (19.7%), limonene (18.7%) and α‐pinene (10.4%) in P. nigrum oil and terpinen‐4‐ol (38.6%) and γ‐terpinene (21.7%) in M. alternifolia oil. The broad‐spectrum antimicrobial activity was achieved by tested three EOs, with C. limon oil being the strongest against bacteria and M. alternifolia oil strongest against fungi. The EOs demonstrated synergism; their combined application revealed an increase in antimicrobial activity. All tested essential oils showed lower cytotoxic activity in comparison with the positive control, and the obtained results confirmed a dose‐dependent activity.
Conclusions
The results of this study encourage use of tested EOs in development of a novel agent intended for prevention or therapy of corresponding oral disorders.
The current study aimed to phytochemically characterize (including a detailed phenolic profile) two endemic Balkan's species (Hieracium waldsteinii and Onosma stellulata) and determine their possible ...application as a source of natural antioxidant and antimicrobial agents. The main phenolic compound in both species (in all examined parts) was chlorogenic acid. Eriodictyol, genistein and naringenin were quantified only in H. waldsteinii while isorhamnetin‐3‐O‐rutinoside and sinapic acid were characteristic for O. stellulata. The highest antioxidant activity (98 mg AAE/g dry weight for TAC assay) was ascribed to the flower extract of H. waldsteinii while the lowest results (∼4.3 mg AAE/g dry weight for FRP assay) were exhibited by the extracts obtained from the plant's stem. Antimicrobial assays showed moderate antibacterial, i. e., moderate/strong activity against several tested fungi (in particular Trichoderma viride). Correlation analysis revealed strong positive connection between phenolic compounds and reducing power of extracts as well as between total phenolic and flavonoid content and the obtained minimal inhibitory concentration recorded in antibacterial assays.
Cilj ove disertacije bio je ispitivanje potencijala antiproliferativnog i in vitro antimetastatskog dejstva serije novosintetisanih rutenijum(II)-arenskih kompleksa. U pitanju je serija ...Ru(II)-arenskih kompleksa sledeih strukturnih formula: (6-pcimen) Ru(L1–3)Cl 2, gde je L1–3: 3-acetilpiridin (1), 4-acetilpiridin (2) i 2-amino-5- hloropiridin (3), kao i (6-p-cimen)Ru(HL4,5)Cl2, gde HL4 i HL5 odovara izonikotinskoj kiselini (4) i nikotinskoj kiselini (5) i (6-p-cimen)Ru(HL6–9)Cl, gde H 2 L6–9 predstavlja 2,3-piridindikarboksilnu kiselinu (6), 2,4-piridindikarboksilnu kiselinu (7), 2,5-piridindikarboksilnu kiselinu (8) i 2,6- piridindikarboksilnu kiselinu (9), i (6-p-cimen)RuCl(L11), gde je HL11 pikolinska kiselina (11). Kompleks (10) je polazni kompleks (6-p-cymene) 2 RuCl 2 2 koji je korišen za sinteze navedenih kompleksa u reakciji sa odgovarajuim ligandima. Antiproliferativna aktivnost Ru(II)- arenskih kompleksa je ispitana na: šest tumorskih elijskih linija (HeLa, MDA-MB-361, MDA-MB-453, FemX, B16, LS-174), na dve transformisane endotelijalne linije (EA.hy 926, MS1) i na jednoj normalnoj humanoj liniji (MRC-5). Za dalja ispitivanja poreenja povezanosti strukture i aktivnosti odabrana su dva kompleksa sa monodentatno vezanim piridinskim ligandom (1 i 3) i dva kompleksa sa bidentano vezanim piridinskim ligandom (6 i 7), koji nisu imali znaajnu citotoksinu aktivnost i pikolinato rutenijum(II)-cimenski kompleks (11), kao kompleks sa znaajnom aktivnošu. Potencijal ispitivanih kompleksa da indukuju promene na nivou elijskog ciklusa odreen je korišenjem protonog citometra nakon bojenja tretiranih elija sa propidijum-jodidom. Takoe, korišenjem testa za detekciju rane faze apoptoze,dvokolornim bojenjem elija sa aneksinom i propidijum-jodidom i analize na protonom citometru ispitan je potencijal kompleksa 11 da indukuje apoptozu. Distribucija rutenijuma(II) u proteinskoj i DNK frakciji HeLa elija tretiranih sa ispitivanim kompleksima utvrena je korišenjem indukovano kuplovane plazme sa optiko emisionom spektrometrijom (ICP-OES).Kako bismo utvrdili da li ispitivani kompleksi indukuju odgovor ćelije zavisan od DNK reparacije kao rezultat interakcija sa DNK, ispitivali smo mRNK (koristeći Kvantitativnu lančanu reakciju polimeraze u realnom vremenu) i proteinski nivo (koristeći Western blot) ekspresije ERCC1 i MSH- 2, koji predstavljaju najznačajnije elemente NER i MMR reparacionih sistema ćelije. S obzirom da značajan broj rutenijumskih antikancerskih agenasa, pokazuje pre svega dobre antimetastatske karakteristike, in vitroantimetastatski potencijal ispitivanih kompleksa praćen je serijom testova kojima je utvrđen njihov efekat na adheziju, migraciju, invazivnost kroz matrigel, angiogenezu, kao i na aktivnost matriksnih metaloproteinaza (MMP-2 i MMP-9). Efekat kombinovanog tretmana kompleka 11 i inhibitora PARP-a (3-aminobenzamida), kao i klinički relevantnih antikancerskih lekova, cisplatine i paklitaksela, ispitan je na HeLa ćelijama.Ispitivani kompleksi 1-9 nisu pokazali značajnu antiproliferativnu aktivnost do koncentracije od 200 µmol/L. Izuzetak od ove serije je kompleks 11 koji je pokazao citotoksičnu aktivnost na svim ispitivanim ćelijskim linijama nakon 48 i 72 h tretmana, sa IC50 vrednostima u opsegu 36-250 µmol/L. Analizom akumulacije rutenijuma (II) u proteinskoj tj. DNK frakciji tretiranih HeLa ćelija kori ćenjem ICP-OES, utvrđen je značajno vi i nivo kompleksa 11 u DNK frakciji. Kompleks 11 je, takode, indukovao promene na nivou ćelijskog ciklusa HeLa ćelija i to smanjujući procenat ćelija u Gl fazi i indukujući blagi zastoj u S fazi ćelijskog ciklusa, bez apoptotskog efekta nakon 24 h tretmana. Tek nakon 48 h tretmana HeLa ćelija sa ispitivanim kompleksom 11 i kori ćenjem testa za detekciju rane faze apoptoze uočen je ne to veći procenat apoptotičnih ćelija. Kompleks 11je uticao na nivo ekspresije enzima reparacije DNK. ERCC1 i MSH2, i pokazao pojačanu aktivnost u kombinaciji sa inhibitorom PARP-a.
A series of five iron(III) complexes, namely Fe(HL1)Cl2 (1), Fe(HL2)Cl2·1.6H2O (2·1.6H2O), Fe(HL3)(MeOH)Cl2·0.5H2O (3·0.5H2O), Fe(HL4)(MeOH)Cl2·0.5H2O (4·0.5H2O) and Fe(HL4)(DMF)Cl2·0.5Et2O·H2O ...(4′·0.5Et2O·H2O), where H2L1 = l‐proline‐salicylaldehyde–thiosemicarbazone (l‐Pro‐STSC), H2L2 = pyrrolidine‐substituted l‐Pro‐STSC, H2L3 = phenyl‐substituted l‐Pro‐STSC, and H2L4 = naphthyl‐substituted l‐Pro‐STSC, have been synthesized. The two ligand precursors (H2L3 and H2L4) and iron complexes were characterized by elemental analysis, spectroscopic methods (UV/Vis, IR, and NMR), ESI mass spectrometry, cyclic voltammetry, and single‐crystal X‐ray crystallography (1–3 and 4′). Magnetic properties of the five‐coordinate complex 2 and six‐coordinate complex 4 have also been investigated. The antiproliferative activity of the organic hybrids and their iron(III) complexes have been studied in vitro in five human cell lines and one murine cancer cell line, namely HeLa (cervical cancer), FemX (melanoma), A549 (alveolar basal adenocarcinoma), LS‐174 (colon cancer), MDA‐MB‐453 (breast cancer) and MS1 (transformed murine endothelial), as well as in human noncancerous fetal lung fibroblast cell line (MRC‐5). According to the structure–activity relationship, introduction of aromatic groups such as phenyl or naphthyl enhances the cytotoxic potency of the hybrids in the following order H2L1 < H2L2 < H2L3 < H2L4. Coordination of the hybrids to iron(III) improves their antiproliferative activity in the majority of investigated cell lines with exception of H2L3 in LS‐174, H2L4 in MS1, and both H2L3 and H2L4 in FemX cell lines, where an opposite effect was observed.
N‐substituted thiosemicarbazone–proline hybrids and their iron(III) complexes were synthesized and characterized. The antiproliferative activity of all hybrids and iron(III) complexes was investigated in five human cancer cell lines and one murine cancer cell line. Introduction of aromatic groups and coordination to iron(III) increase the cytotoxic potential of the proligands.
A series of six imidazole-derived thiosemicarbazones ( HL1–HL6 ) and their copper( ii ) complexes ( 1–6 ) were synthesised and characterised by analytical, spectroscopic, electrochemical and single ...crystal X-ray diffraction techniques. In addition, solution studies and the results of antiproliferative activity in human cancer cell lines with some insights into the mechanism of cancer cell death are also reported. In particular, the substitution of one hydrogen at the terminal N-atom of the thiosemicarbazide moiety by a phenyl group resulted in slightly enhanced antiproliferative activity. HL3 and HL6 showed lower IC 50 values compared to HL1 and HL4 in MDA-MB-453 and LS174 cancer cell lines. The copper( ii ) complexes 3 and 6 exhibit a 2.4- and 4.7-fold increase of activity compared to parent proligands in MDA-MB-453 cancer cell line, respectively. The complex formation of the proligands with copper( ii ) increased their antiproliferative activity in all investigated cell lines. The cell cycle perturbations, apoptotic potential and the analysis of morphological changes in the A549 cell line induced by 3 and 6 revealed cytostatic rather than cytotoxic effects.
A ruthenium(II)-arene complex with picolinic acid, ( eta super(6)-p-cyme-ne)RuCl(pico) times H sub(2)O, was prepared by the reaction of ( eta super(6)-p-cymene)RuCl sub(2) sub(2) with picolinic acid ...in a 1:2 molar ratio in 2-propanol. The compound was characterized by elemental analysis, and IR and NMR spectroscopy. X-ray diffraction analysis showed that the molecule adopts a "three-leg piano-stool" geometry, which is common for this type of complexes. The cytotoxic activity of the complex was tested in two human cancer cell lines HeLa (cervix) and FemX (melanoma) by MTT assay. The IC sub(50) values were at 82.0 and 36.2 mu mol dm super(-3) for HeLa and FemX cells, respectively.
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