Investigation of interactions of biologically active quinone avarone and its derivates with lysozyme, linear and circular deoxyribonucleic acid

Cilj našeg rada bio je ispitivanje biološke aktivnosti metilamino- i metoksiderivata avarona i razjašnjavanje mehanizma njihovog biološkog dejstva. Za sintezu su izabrani derivati za koje se očekivalo da će imati negativniji polutalasni potencijal od avarona i samim tim pokazivati povećanu aktivnost. Sintetisani su 4'-(metilamino)-avaron, 3'-(metilamino)-avaron i 3'-metoksi-avaron. Antibakterijska aktivnost dobijenih derivata je ispitivana prema gram-pozitivnim bakterijama: Bacillus subtilis, Clostridium sporogenes, Streptosporangium longisporum, Micrococcus flavus, Sarcina lutea i Staphylococcus aureus, prema gramnegativnim bakterijama: Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enteritidis, Escherichia coli i prema kulturama gljivica: Aspergillus niger, Candida albicans i Saccharomyces cerevisiae disk-difuzionom metodom. Takođe, ispitivana je i toksičnost derivata na račiće Artemia salina. Potencijalna antioksidativna aktivnost avarona i dobijenih derivata ispitivana je testom sa DPPH. Antitumorska aktivnost ispitivana je za sve derivate na osam vrsta ćelija raka (ćelijske linije raka grlića materice, melanoma i leukemije, rak dojke pozitivan na estrogeni receptor, rak dojke negativan na estrogeni receptor, rak pluća, leukemija T-ćelija i promijelocitna leukemija) pri čemu je ispitivana i njihova citotoksičnost na limfocite. Svim hinonskim derivatima hemijski je modifikovan model-enzim lizozim. Dobijenim modifikatima lizozima je nakon modifikacije određena enzimska aktivnost. Sama modifikacija je praćena UV/Vis spektrofotometrijom, SDS elektroforezom i masenom spektrometrijom. Mesto vezivanja hinonskih derivata za molekul lizozima određeno je tehnikom MALDI TOF posle tripsinske digestije modifikata. S obzirom na uočeno vezivanje avaronskih derivata za ε-amino grupu lizina (Lys-97) u lizozimu, sintetisano je jedinjenje 4'-((5-tert-butoksikarbonil)amino)-5-karboksipentil)amino)- avarona, koje je poslužilo kao model jedinjenje za dalja ispitivanja biološke aktivnosti lizozim-hinonskog adukta...aim of our work has been investigation of biological activity of methylamino- and metoxy- derivatives of avarone, their bioconjugates of lysozyme and study of the mechanism of their biological action. For synthesis were chosen derivatives for which it was expected to have more negative half-wave potential than avarone and therefore a higher activity. The selected compounds are 3’-methylamino, 4’-methylamino- and 3’-methoxyavarone. Antimicrobial activity of the synthesized derivatives was investigated towards Gram positive bacteria: Bacilus subtilis, Clostridium sporogenes, Sreptosporangium longisporum., Micrococcus flavus, Sarcina lutea and Staphylococcus aureus, Gram negative bacteria: Klebsiella pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella enteritidis and Escherichia coli and fungi cultures: Aspergilus niger, Candida albicans and Sacharomyces cerevisiae, all by disc diffusion method. Toxicity against Artemia salina nauplii was surveyed as well. Antioxidant activity of avarone and its derivatives was assessed by DPPH assay. Antitumor activity was determined for all derivatives towards eight lines of tumor cells (myelogenous leukemia (K562), cervix carcinoma (HeLa), human malignant melanoma cells (Fem-X), Jurkat T cell leukemia, estrogen receptor negative breast carcinoma (MDA-MB-231), estrogen receptor positive breast carcinoma (MCF7), human fetal lung fibroblast (MRC-5) and human promyelocytic leukemia (HL-60)). For all derivatives toxicity towards lymphocytes was determined. Model enzyme lysozyme was modified with the synthesized quinones and for all the obtained bioconjugates MIC value towards Gram positive and Gram negative bacteria were determined. Modification reaction was monitored by UV/VIS spectrophotometry, SDS electrophoresis and mass spectrometry. Binding position of quinone derivatives on lysozyme was determined by MALDI TOF spectrometry after trypsin digestion. Since the avarone derivatives were found to bind to lysine (Lys-97) in lysozyme, 4’-((5-((tert-butoxycarbonyl)amino)-5-carboxypentyl)-amino)avarone has been synthesized as a model compound for further investigation of the biological activity of lysozyme―quinone aduct..

Sinteza, karakterizacija i procena antioksidativne i antimikrobne aktivnosti tri nova n-heteroaromatična hidrazonil-tiazola

(Thiazolyl-2-yl)hydrazones (THs) are a group of organic compounds containing both hydrazone and 1,3-thiazole pharmacophores present in many approved drugs. They have been investigated greatly in recent years due to potent anticancer, antibacterial, antifungal, antituberculosis, anti-inflammatory, and antiparasitic activities. In this study, one pyridine-based and two quinoline-based, novel THs were synthesized and characterized by elemental analysis, Fourier-transform infrared spectroscopy (FTIR), and nuclear magnetic resonance spectroscopy (NMR). The antimicrobial activity of the compounds was tested against five Gram-positive and five Gram-negative bacteria, as well as against three fungi. The antioxidant capacity of the compounds was tested in six antioxidative assays. The results showed that quinoline-based THs were more active against tested Gram-negative bacteria and fungi strains than pyridine-based compounds. All the compounds showed excellent antioxidative activity comparable to or greater than the used standards (vitamin C and Trolox). Absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were calculated in-silico. Results pointed to promising good pharmacokinetics profiles of investigated compounds, especially 2-quinoline carboxaldehyde-based compound, which can be a lead drug candidate.(Tiazolil-2-il)-hidrazoni (TH) su grupa organskih jedinjenja koja sadrže i hidrazon i 1,3-tiazol farmakofore koje su prisutne u mnogim odobrenim lekovima. Poslednjih godina se u velikoj meri istražuju zbog jakih antikancerogenih, antibakterijskih, antifungalnih, antituberkuloznih, antiinflamatornih i antiparazitskih aktivnosti. U ovoj studiji, sintetisan je jedan novi TH na bazi piridina i dva na bazi hinolina, koji su okarakterisani elementalnom analizom, infracrvenom spektroskopijom sa Furijeovom transformacijom (FTIR) i spektroskopijom nuklearne magnetne rezonancije (NMR). Antimikrobna aktivnost jedinjenja je testirana na pet Gram-pozitivnih i pet Gram-negativnih bakterijskih sojeva, kao i na tri soja gljivica. Šest antioksidativnih testova je korišćeno za određivanje antioksidativnog kapaciteta sintetisanih jedinjenja. Rezultati su pokazali da su TH na bazi hinolina aktivniji prema testiranim Gram-negativnim sojevima bakterija i prema gljivicama, nego jedinjenja na bazi piridina. Sva jedinjenja su pokazala odlično antioksidativno dejstvo, uporedivo ili veće od korišćenih standarda (vitamin C i troloks). Parametri apsorpcije, distribucije, metabolizma, izlučivanja i toksičnosti (ADME) izračunati su in-silico. Rezultati ukazuju na dobre farmakokinetičke profile ispitivanih jedinjenja, posebno jedinjenja na bazi 2-hinolinkarboksaldehida koje ima potencijal da bude kandidat za osnovno jedinjenje (engl. lead compound)

Synthesis and investigation of biological activity of arylthio and aralkylthio derivatives of 2-tert-butyl-1.4-benzoquinone

Sintetisana su dva ariltio i dva aralkiltio derivata 2-terc-butil-1,4-benzohinona reakcijom Michael-ove adicije tiola na hinonsko jezgro u etanolu. Dobijenim derivatima je ispitana antimikrobna i antioksidativna aktivnost, kao i toksinost na raie Artemia salina. Najjau antimikrobnu aktivnost je pokazao derivat 4, najveu antioksidativnu aktivnost je imao derivat 2 (IC50=0,0526 mM), dok je toksinost prema raiima ispoljio samo derivat 4 (LC50=0,032 mM).Two arylthio and aralkylthio derivatives of 2-tert-butyl-1.4-benzoquinone were synthesized by Michael addition of thiols on quionone moiety in ethanol. For all compounds antimicrobial and antioxidant activity was investigated, as well as toxicity towards nauplii of Artemia salina. Derivative 4 showed the strongest antimicrobial activity, derivative 2 showed the most intense antioxidant activity (IC50=0.0526 mM), while only derivative 4 showed toxicity against nauplii of A. salina (LC50=0.032 mM)

Supplementary data for the article: Dimitrijević, T.; Novaković, I.; Radanović, D.; Novaković, S. B.; Rodić, M. V.; Anđelković, K.; Šumar-Ristović, M. Synthesis, Spectral and Structural Characterization and Biological Activity of Cu(II) Complexes with 4-(Diethylamino)Salicylaldehyde and α-Diimines. Journal of Coordination Chemistry 2020, 73 (4), 702–716. https://doi.org/10.1080/00958972.2020.1740212

Supplementary material for: [https://doi.org/10.1080/00958972.2020.1740212]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/4025

Dobijanje i karakterizacija dva tipa imobilizovane amiloglukozidaze

Amyloglucosidase from A. niger was covalently immobilized onto poly(GMA-co-EGDMA) by the glutaraldehyde and periodate method. The immobilization of amyloglucosidase after periodate oxidation gave a preparate with the highest specific activity reported so far on similar polymers. The obtained immobilized preparates show the same pH optimum, but a higher temperature optimum compared with the soluble enzyme. The kinetic parameters for the hydrolysis of soluble starch by free and both immobilized enzymes were determined.Amiloglukozidaza iz A.niger je imobilizovana na poly(GMA-co-EGDMA) glutaraldehidnom i perjodatnom metodom. Imobilizacija amiloglukozidaze nakon perjodatne oksidacije daje preparat sa najvećom do sada objavljenom specifičnom aktivnosti na sličnim polimerima. Dobijeni imobilizovani preparat ima isti pH optimum ali povećani termooptimum u poređenju sa rastvornim enzimom. Određeni su i kinetički parametri za hidrolizu rastvornog skroba imobilizovanim kao i rastvornim enzimom

Supplementary material for the article: Vilipić, J. P.; Novaković, I. T.; Zlatović, M. V.; Vujčić, M. T.; Tufegdžić, S. J.; Sladić, D. M. Interactions of Cytotoxic Amino Acid Derivatives of Tert-Butylquinone with DNA and Lysozyme. Journal of the Serbian Chemical Society 2016, 81 (12), 1345–1358. https://doi.org/10.2298/JSC160725101V

Supplementary material for: [https://doi.org/10.2298/JSC160725101V]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2389

Electrochemically exfoliated graphene as support of platinum nanoparticles for methanol oxidation reaction and hydrogen evolution reaction

To enhance the utilization efficiency of platinum (Pt) in electrochemical energy conversion, the precise selection of support materials presents a highly promising strategy. We have developed an efficient and stable bifunctional catalyst for methanol oxidation (MOR) and hydrogen evolution (HER) reaction in an alkaline medium. The Pt-based electrocatalyst, denoted as Pt/e-rGO with low Pt loading was successfully synthesized using graphene sheets as the support via chemical reduction using formic acid as the reducing agent. Graphene sheets are obtained by anodic electrochemical exfoliation of graphite tape. Significant enhancement of intrinsic activity toward MOR and HER was achieved for Pt/e-rGO compared to the commercial Pt/C catalyst. Structural characterization was performed by TEM, SEM and XPS. XPS analysis shows that the graphene is highly reduced. TEM analysis unveiled that the majority of the Pt nanoparticles (NPs) exhibit a diameter in the range of 4-5 nanometers, which is significant because the efficiency of electrooxidation of methanol on supported Pt NPs shows a strong dependence on particle size distribution. Catalyst activity was studied by cyclic voltammetry and linear sweep voltammetry in 0.1M KOH. Electrochemical active surface area (ECSA) was measured by CO-stripping voltammetry and estimated to be 67.93 m2 /g. Current density of 11.28 mA/cm2 ECSA at 0.82 V vs. RHE for MOR is achieved. Onset potential for MOR is 0.55 V vs. RHE. Meanwhile, for HER overporential at the current density -10 mA/cm2 ECSA was 119 mV.Twenty-First Young Researchers’ Conference - Materials Science and Engineering: Program and the Book of Abstracts; November 29 – December 1, 2023, Belgrade, Serbi

Supplementary data for article: Krstić, N. M.; Pavlović, V. D.; Novaković, I. T.; Matić, I. Z.; Sladić, D. Synthesis, Characterization and Biological Evaluation of Some Novel P-Heterocyclic Androst-4-Ene Derivatives. Molecular Diversity 2013, 17 (3), 547–561. https://doi.org/10.1007/s11030-013-9455-9

Supplementary material for: [https://doi.org/10.1007/s11030-013-9455-9]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1376

Composition, Antioxidant Potential, and Antimicrobial Activity of Helichrysum plicatum DC. Various Extracts

Helichrysum plicatum DC. is widely used in folk medicine in treating a variety of health disorders. The aim of this study was to examine the influence of different extraction solvents on the chemical composition, antioxidant potential, and antimicrobial activities of H. plicatum. Aerial parts were separately extracted with ethanol, dichloromethane, and sunflower oil. The oil extract (OE) was re-extracted with acetonitrile. A total of 142 compounds were tentatively identified in ethanolic (EE), dichloromethane (DCME), and acetonitrile (ACNE) extracts using HPLC-DAD/ESI-ToF-MS. The dominant compound class in all extracts were α-pyrones, alongside flavonoids in EE, terpenoids in DCME and ACNE, and phloroglucinols in DCME. The antioxidant potential of the extracts was assessed by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay. EE and DCME possessed the most potent radical scavenging capacity. Antimicrobial activity was investigated on eight bacterial, two yeast, and one fungal species. All extracts exhibited high antifungal and notable antibacterial activities compared to control substances, with DCME being the most potent. DCME exhibited stronger antimicrobial activity against P. aeruginosa than the standard chloramphenicol

Supplementary data for the article: Sović, I.; Cindrić, M.; Perin, N.; Boček, I.; Novaković, I.; Damjanović, A.; Stanojković, T.; Zlatović, M.; Hranjec, M.; Bertoša, B. Biological Potential of Novel Methoxy and Hydroxy Substituted Heteroaromatic Amides Designed as Promising Antioxidative Agents: Synthesis, 3D-QSAR Analysis, and Biological Activity. Chemical Research in Toxicology 2019, 32 (9), 1880–1892. https://doi.org/10.1021/acs.chemrestox.9b00256

Supplementary material for: [https://doi.org/10.1021/acs.chemrestox.9b00256]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3851]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3914