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 data for article: Cvijetić, I.; Vitorović-Todorović, M. D.; Juranić, I. O.; Drakulić, B. J. Reactivity of (E)-4-Aryl-4-Oxo-2-Butenoic Acid Arylamides toward 2-Mercaptoethanol. A LFER Study. Monatshefte Fur Chemie 2013, 144 (12), 1815–1824. https://doi.org/10.1007/s00706-013-1084-6

Supplementary material for: [https://doi.org/10.1007/s00706-013-1084-6]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1441

Molekulsko-orbitalno proučavanje oksidacije fenola u hinole i epoksihinole

The MO study showed that the radical oxidation of phenols into quinols occurs readily. Further radical oxidation (in the m-CPBA/(BzO)(2)/hv system) of quinols occurs through appropriate biradical species with an activation energy of 79.5 kJ/mol yielding syn-epoxyquinols. The stereochemical outcome presented in this study is in full agreement with the experimental results.Molekulsko-orbitalnim proučavanjem potvrđeno je da lako dolazi do radikalske oksidacije fenola u odgovarajuće hinole. Daljom oksidacijom sistemom m-CPBA/(BzO)2/hν hinoli se preko biradikalskih reakcionih vrsta oksiduju u odgovarajuće epoksihinole. Izračunato je da aktivaciona energija ove reakcije iznosi 79.5 kJ/mol. Stereohemijske posledice naših izračunavanja su u potpunom skladu sa eksperimentalnim rezultatima

Supplementary data for the article: Vitorović-Todorović, M. D.; Koukoulitsa, C.; Juranić, I. O.; Mandić, L. M.; Drakulić, B. J. Structural Modifications of 4-Aryl-4-Oxo-2-Aminylbutanamides and Their Acetyl- and Butyrylcholinesterase Inhibitory Activity. Investigation of AChE-Ligand Interactions by Docking Calculations and Molecular Dynamics Simulations. European Journal of Medicinal Chemistry 2014, 81, 158–175. https://doi.org/10.1016/j.ejmech.2014.05.008

Supplementary material for: [https://doi.org/10.1016/j.ejmech.2014.05.008]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1808]Related to accepted version:[http://cherry.chem.bg.ac.rs/handle/123456789/2907

Supplementary data for the article: Cvijetić, I. N.; Tanç, M.; Juranić, I. O.; Verbić, T. Ž.; Supuran, C. T.; Drakulić, B. J. 5-Aryl-1H-Pyrazole-3-Carboxylic Acids as Selective Inhibitors of Human Carbonic Anhydrases IX and XII. Bioorganic and Medicinal Chemistry 2015, 23 (15), 4649–4659. https://doi.org/10.1016/j.bmc.2015.05.052

Supplementary material for: [https://doi.org/10.1016/j.bmc.2015.05.052]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1742]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3327

Human Serum Albumin Binding of 2-[(Carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic Acid and its Mono-Me Ester

Interactions of 2-[(carboxymethyl)sulfanyl]-4-oxo-4-(4-tert-butylphenyl)butanoic acid (compound 1) and its mono-Me ester (compound 2) with the human serum albumin (HSA) have been studied by fluorescence spectroscopy. Comp. 1 exerts antiproliferative activity toward human tumor cells and significant selectivity (tumor vs. healthy cells) in vitro. Competitive binding study with warfarin and ibuprofen as binding site probes, revealed that one molecule of comp. 1 selectively binds to HSA Sudlow site I (warfarin site) with moderate binding constant (Kb = (2.8 ± 0.5) x 104 M-1 at 37 ± 1 oC), while comp. 2 binds to Sudlow site II (Kb = (3.2 ± 0.9) x 104 M-1 at 37 ± 1 oC). Fluorescence quenching at different temperatures was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. Energy resonance transfer between HSA and comp. 1 was examined according to Förster’s non-radiative energy transfer theory. Distance of about 10 Å between ligand and Trp214 (HSA) was obtained. Docking studies confirmed HSA Sudlow site I as a preferable comp. 1 binding site, and Sudlow site II as comp. 2 binding site. Molecular dynamics simulations proved the stability of comp. 1/HSA complex

Conformational preferences of 2-[(2-hydroxyethyl)sulfanyl]-4-oxo-4-(2,4-diisopropylphenyl)- butanoic acid phenylamide. The NMR/MD study

Title molecule, recently prepared in our laboratory comprises the pharmacophoric pattern of the BH3 domain inhibitors. Such compounds were extensively studied as the antiproliferative agents. In this communication we present its conformational preferences in the solvents of different polarity and HBD/HBA abilities. NOESY spectra of compound were recorded in DMSO-d6 and CDCl3. NOESY cross-peaks and coupling constants were processed by NAMFIS analysis and results compared with the conformational assembly and the free-energy surfaces of compound obtained by molecular dynamics simulations in the corresponding explicit solvents. Adaptive biasing force was used to map free-energy surfaces. Janocchio program was used for the NAMFIS analysis, molecular dynamics simulations (30 ns, each) were performed in NAMD 2.9 using CHARMm22 force field on the multi-node Linux cluster. Conformations of the compound were generated by OMEGA program.Прва конференција младих хемичара Србије, Београд 19-20. Октобар 2012

Antiproliferative activity of β-hydroxy- β-arylalkanoic acids

Article describes the synthesis of fifteen β-hydroxy- β-arylalkanoic acids by Reformatsky reaction using the 1-ethoxyethyl-2- bromoalkanoates, aromatic or cycloalkyl ketones or aromatic aldehydes. The short survey of previously reported synthetic procedures for title compounds, is given. The majority of obtained compounds exert antiproliferative activity in vitro toward human: HeLa, Fem-X cells, K562, and LS174 cells, having IC 50 values from 62.20 to 205 μM. The most active compound is 3-OH-2,2-di-Me-3-(4-biphenylyl)-butanoic acid, having the IC 50 value 62.20 μM toward HeLa cells. Seven examined compounds did not affect proliferation of healthy human blood peripheral mononuclear cells (PBMC and PBMC+ PHA), IC 50 > 300 μM. The preliminary QSAR results show that estimated lipophilicity of compounds influences their antiproliferative activity in the first place. The ability of dehydration, and the spatial arrangement of hydrophobic portion, HBD and HBA in molecules are has almost equal importance as lipophilicity

Optimizacija sinteze i in vitro proučavanje antimikrobnog dejstva α,β-nezasićenih i α-bromkarboksilnih kiselina

A series of α,β-unsaturated and α-bromo carboxylic acids were identified as potent antimicrobial agents. The antimicrobial activity was evaluated using the broth microdilution method. All acids 1-12 exhibited a significant activity against nine laboratory control strains of bacteria and two strains of yeast Candida albicans. The tested acids were efficiently prepared by optimized phase-transfer-catalyzed (PTC) reactions of ketones with bromoform and aqueous lithium hydroxide in alcoholic solvent with triethylbenzyl ammonium chloride (TEBA) as catalyst.U ovom radu je prikazano in vitro ispitivanje antimikrobnog dejstva serije α,β-nezasićenih i α-bromkarboksilnih kiselina i pokazano je da su one potencijalno dobri antimikrobni agensi. Sve kiseline 1-12 pokazale su značajnu aktivnost prema devet sojeva bakterija i dva soja gljivica Candida albicans. Ispitivane kiseline sintetisane su u optimizovanoj reakciji ketona sa bromoformom i litijum-hidroksidom u smesi rastvarača (terc-butanol/voda). Kao katalizator za prenos između faza upotrebljen je trietilbenzilamonijum-hlorid (TEBA)

Određivanje pKa vrednosti i korelacija sa strukturom p-supstituisanih trans-2,3-epoksi-4-okso-4-fenilbutanskih kiselina

The pKa values for a series of eight p-substituted trans-2,3-epoxy-4-phenyl butanoic acids (p-substituted trans-β-aroylepoxyacrylic acids) have been determined potentiometrically in aqueous media at 25 °C at an ionic strength of 0.1 mol/dm3 (NaCl). The transmission of polar effects from the substituents on the phenyl nucleus to the carboxylic group through the side chain involving a carbonyl group and an epoxide ring was investigated. The pKa values were correlated with structure using the Hammett, Taft and Yukawa-Tsuno approaches. The Hammett ρ constant (0.34) was compared with analogue values for structurally similar acids.Određene su pKa vrednosti za seriju od osam p-supstituisanih trans-2,3-epoksi-4-okso-4-fenilbutanskih kiselina (p-supstituisanih trans-β-aroilepoksiakrilnih kiselina). Vrednosti su određene potenciometrijski u vodenoj sredini na 25 °C i jonskoj sili 0.1 mol/dm3 (NaCl). Proučavan je prenos polarnih efekata sa supstituenata na fenil jezgru ka karboksilnoj grupi kroz bočni niz koji sadrži karbonilnu grupu i epoksidni prsten. pKa vrednosti su korelisane sa strukturom primenom Hammett-ovog, Taft-ovog i Yukawa-Tsuno-ovog pristupa. Hammett-ova ρ konstanta (0,34) je upoređena sa analognim vrednostima za strukturno slične kiseline