Ratomir Jelic
@kg.ac.rs
Faculty of Medical Sciences University of Kragujevac
Faculty of Medical Sciences University of Kragujevac
RESEARCH, TEACHING, or OTHER INTERESTS
General Chemistry, Inorganic Chemistry, Analytical Chemistry, Spectroscopy
Scopus Publications
Scopus Publications
Marina Vesović, Ratomir Jelić, Miloš Nikolić, Nikola Nedeljković, Ana Živanović, Andriana Bukonjić, Emina Mrkalić, Gordana Radić, Zoran Ratković, Jakob Kljun,et al.
Informa UK Limited
S-isoalkyl derivatives of thiosalicylic acid (isopropyl-(L1), isobutyl-(L2) and isoamyl-(L3)) were selected in order to investigate the binding interaction with the human serum albumin (HSA) using different spectroscopic methods and molecular docking simulation. Association constants and number of binding sites were used to analyze the quenching mechanism. The experimental results showed that the fluorescence quenching of HSA by L1, L2 and L3 occurs because of static quenching and that binding processes were spontaneous, with the leading forces in bonding by hydrogen bonding, hydrophobic interactions, and electrostatic interactions. Fluorescence spectroscopy, UV-Vis spectroscopy and synchronous fluorescence spectroscopy showed that ligands (L1, L2 and L3) can bind to HSA and that the binding of ligands induced some microenvironmental and conformational changes in HSA. The calculated distance between the donor and the acceptor according to fiFörster's theory confirms the energy transfer efficiency between the acceptor and HSA. Results of site marker competitive experiments showed that the tested compounds bind to HSA in domain IIA (Site I). Molecular dynamics and docking calculations demonstrated that L3 binds to the Sudlow site I of HSA with lower values of binding energies compared to L1 and L2, indicating the formation of the most stable ligand-HSA complex. Understanding the binding mechanisms of S-isoalkyl derivatives of the thiosalicylic acid to HSA may provide valuable data for the future studies of their biological activity and application as potential antitumor drugs.Communicated by Ramaswamy H. Sarma.
Tanja V. Soldatović, Biljana Šmit, Emina M. Mrkalić, Sanja Lj. Matić, Ratomir M. Jelić, Marina Ćendić Serafinović, Nevenka Gligorijević, Milena Čavić, Sandra Aranđelović, and Sanja Grgurić-Šipka
Elsevier BV
Edina H. Avdović, Žiko B. Milanović, Krešimir Molčanov, Sunčica Roca, Dražen Vikić-Topić, Emina M. Mrkalić, Ratomir M. Jelić, and Zoran S. Marković
Elsevier BV
Miroslav Sovrlić, Emina Mrkalić, Ratomir Jelić, Marina Ćendić Serafinović, Stefan Stojanović, Nevena Prodanović, and Jovica Tomović
MDPI AG
Human serum albumin (HSA) has a very significant role in the transport of drugs, in their pharmacokinetic and pharmacodynamic properties, as well as the unbound concentration of drugs in circulating plasma. The aim of this study was to look into the competition between tigecycline (TGC) and alkaloid (ALK) (caffeine (CAF)), and flavonoids (FLAVs) (catechin (CAT), quercetin (QUE), and diosmin (DIO)) in binding to HSA in simulated physiological conditions using multiple spectroscopic measurements and docking simulations. Fluorescence analysis was used to find the binding and quenching properties of double HSA-TGC and triple HSA-TGC-CAF/FLAV systems. The conformational change of the HSA was analyzed using synchronous fluorescence spectroscopy, Fourier transform infrared spectroscopy, and circular dichroism. Obtained results of spectroscopic analyses indicate that triple complexes of HSA-TGC-CAF/FLAVs are formed without problems and have higher binding affinities than double HSA-TGC. In addition, TGC does not change the microenvironments around the tryptophan (Trp) and tyrosine (Tyr) residues in the presence of ALK and FLAVs. Ultimately, the binding affinity, competition, and interaction nature were explored by docking modeling. Computational outcomes are in good accordance with experimentally obtained results. Accordingly, concluding remarks may be very useful for potential interactions between common food components and drugs.
Đorđe S. Petrović, Sandra S. Jovičić Milić, Maja B. Đukić, Ivana D. Radojević, Ratomir M. Jelić, Milena M. Jurišević, Gordana P. Radić, Nevena M. Gajović, Nebojša N. Arsenijević, Ivan P. Jovanović,et al.
Elsevier BV
Emina Mrkalić, Ratomir Jelić, Stefan Stojanović, and Miroslav Sovrlić
Elsevier BV
Sovrlic Miroslav, , Jelic Ratomir, Antonijevic Marko, Markovic Zoran, Tomovic Jovica, Mrkalic Emina, , , ,et al.
Babes-Bolyai University
Maja B. Đukić, Marija S. Jeremić, Ignjat P. Filipović, Olivera R. Klisurić, Vesna V. Kojić, Dimitar S. Jakimov, Ratomir M. Jelić, Valentina Onnis, and Zoran D. Matović
Elsevier BV
Dušan Ćoćić, Snežana Jovanović-Stević, Ratomir Jelić, Sanja Matić, Suzana Popović, Predrag Djurdjević, Dejan Baskić, and Biljana Petrović
Royal Society of Chemistry (RSC)
Dinuclear complexes [Pd2(tpbd)Cl2]Cl2, [Pt2(tpbd)Cl2]Cl2 and [PdPt(tpbd)Cl2]Cl2 (tpbd = N,N,N′,N′-tetrakis(2-pyridylmethyl)benzene-1,4-diamine) have been synthesized and the kinetic, interactions with DNA/BSA and cytotoxic activity were studied.
Maja B. Djukić, Marija S. Jeremić, Ignjat P. Filipović, Olivera R. Klisurić, Ratomir M. Jelić, Suzana Popović, Sanja Matić, Valentina Onnis, and Zoran D. Matović
Wiley
Stefan D. Stojanović, Jovan M. Nićiforović, Sandra M. Živanović, Jadranka V. Odović, and Ratomir M. Jelić
Springer Science and Business Media LLC
Jelena D. Berić, Stefan D. Stojanović, Emina M. Mrkalić, Zoran D. Matović, Dragan R. Milovanović, Miroslav M. Sovrlić, and Ratomir M. Jelić
Springer Science and Business Media LLC
Marija S. Jeremić, Marko D. Radovanović, Franco Bisceglie, Vesna V. Kojić, Ratomir Jelić, and Zoran D. Matović
Elsevier BV
Maja Djukić, Marija S. Jeremić, Ratomir Jelić, Olivera Klisurić, Vesna Kojić, Dimitar Jakimov, Predrag Djurdjević, and Zoran D. Matović
Elsevier BV
Zoran Jovanovic, Vesela Radonjic, Ratomir Jelic, Narcisa Petrovic-Subic, Ivan Soldatovic, Vera Terzic, Sladjan Stojilkovic, and Dusan Djuric
Centre for Evaluation in Education and Science (CEON/CEES)
Abstract Apart from providing knowledge on the beneficial effects of drugs, practical psychopharmacotherapy also includes drug profiles of adverse effects, especially when medical comorbidity is present. The mechanism of action of many psychotropic drugs, mainly antipsychotics and antidepressants, is associated with prolongation of the QT interval and the occurrence of arrhythmias, specifically Torsade de pointes (TdP), which can be lethal. The aim of this pilot study was to confirm the prevalence of prolonged QTc interval in a sample of psychiatric patients taking psychopharmacs. The present study included 41 patients who were already on psychopharmacs. The average value of the QTc interval in the observed sample was 413.8±23.3 ms. The most frequent psychopharmacotherapy was the combination of typical and atypical antipsychotics (24.4%), followed by monotherapy with antipsychotics (22%) and combined antidepressant and atypical antipsychotic therapy (22%). The average value of the QTc interval for male patients was 412.1±25.2 ms, whereas for female patients, it was 416.6±20.4 ms. No difference between sexes was confirmed (p=0.555). The correlation between the QTc interval and age of patients was positive but not statistically significant (p=0.072). The highest average (419.3±31.6 ms) and highest maximum (479 ms) values of the QTc interval were noted for patients undergoing combined therapy of antidepressants and atypical antipsychotics. Prolonged values of the QTc interval were observed for seven males and one female, and no patients exhibited pathological values. This study confirmed previous research that found that prolongation of the QTc interval exists in patients in sample groups who take psychopharm acs, but not up to critical values.
Ratomir M. Jelic, Stefan D. Stojanovic, Jelena D. Beric, and Jadranka Odovic
Centre for Evaluation in Education and Science (CEON/CEES)
AbstractThe co-administration of several drugs in multidrug therapy may alter the binding of each drug to human serum albumin (HSA) and, thus, their pharmacology effect. Therefore, in this study, the interaction mechanism between HSA and two fluoroquinolones (FQs), sparfloxacin (SPF) and levofloxacin (LVF), was investigated using fluorescence and absorption methods in the absence and presence of the competing drugtigecycline (TGC). The the UV-Vis and fluorescence spectroscopy results showed that the fluorescence quenching of HSA was a result of the formation of the HSA-SPF and HSA-LVF complexes. The fluorescence quenching of HSA-TGC revealed that tigecycline can regulate the binding sites, binding mode and binding affinity of fluoroquinolones. The binding constants (KA) and binding sites (n) of the interaction systems were calculated. The results confirmed that the KAvalues of the HSA-FQ system decreased in the presence of TGC, indicating that TGC can affect the binding ability of FQ for HSA. This interaction may increase the free plasma concentration of unbound FQ and enhance their pharmacology effect.
Danijela Lj. Stojković, Verica V. Jevtić, Gordana P. Radić, Maja B. Đukić, Ratomir M. Jelić, Milan M. Zarić, Marija V. Anđelković, Milena S. Mišić, Dejan D. Baskić, and Srećko R. Trifunović
Royal Society of Chemistry (RSC)
In vitro activity of ligands and corresponding platinum(ii) and palladium(ii) complexes.
Jovana Trbojevic, Jadranka Odovic, Jasna Trbojevic-Stankovic, Biljana Stojimirovic, and Ratomir Jelic
Walter de Gruyter GmbH
Abstract Angiotensin-converting enzyme (ACE) inhibitors modulate the function of the renin-angiotensin-aldosterone system, and they are commonly prescribed antihypertensive drugs especially in patients with renal failure. In this study, the relationships between several molecular properties of eight ACE inhibitors (enalapril, quinapril, fosinopril, ramipril, benazepril, perindopril, moexipril, trandolapril) and their renal elimination data, from relevant literature, were investigated. The ’molecular descriptors of the ACE inhibitors, which included aqueous solubility data (logS); an electronic descriptor, polar surface area (PSA);, a constitutional parameter, molecular mass (Mr); and a geometric descriptor, volume value (Vol), as well as lipophilicity descriptors (logP values), were calculated using different software packages. Simple linear regression analysis showed the best correlation between renal elimination data and lipophilicity descriptor AClogP values (R2 = 0.5742). In the next stage of the study, multiple linear regression was applied to assess a higher correlation between the ACE inhibitors’ renal elimination data and lipophilicity, AClogP, with one additional descriptor as an independent variable. Good correlations were established between renal elimination data from the literature and the AClogP lipophilicity descriptor using the constitutional parameter (molecular mass (R2 = 0.7425)) or the geometric descriptor (volume value (R2 = 0.7224)) as an independent variable. The application of computed molecular descriptors in evaluating drug elimination is of great importance in drug research.
Jelena Beric, Ratomir Jelic, Dejan Nesic, Jasna Trbojevic-Stankovic, and Jadranka Odovic
National Library of Serbia
The plasma protein binding (PPB) data of twelve antipsychotics (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, chlorpromazine, flupentixol, fluphenazine, haloperidol, zuclopenthixol) were estimated using computed molecular descriptors, which included the electronic descriptor ? polar surface area (PSA), the constitutional parameter ? molecular weight (Mw), the geometric descriptor ? volume value (Vol), the lipophilicity descriptor (logP) and aqueous solubility data (logS), and the acidity descriptor (pKa). The relationships between computed molecular properties of the selected antipsychotics and their PPB data were investigated by simple linear regression analysis. Low correlations were obtained between the PPB data of the antipsychotics and PSA, Mw, Vol, pKa, logS (R <0.30) values, while relatively higher correlations (0.35 < R2 < 0.70) were obtained for the majority of logP values. Multiple linear regression (MLR) analysis was applied to access reliable correlations of the PPB data of the antipsychotics and the computed molecular descriptors. Relationships with acceptable probability values (P<0.05) were established for five lipophilicity descriptors (logP values) with application of the acidity descriptor (pKa) as independent variables: AlogP (R2=0.705), XlogP3 (R2=0.679), ClogP (R2=0.590), XlogP2 (R2=0.567), as well as for the experimental lipophilicity parameter, logPexp (R2=0.635). The best correlations obtained in MLR using AlogP and pKa as independent variables were checked using three additional antipsychotics: loxapine, sulpiride and amisulpride, with the PPB values of 97%, ?less than? 40% and 17%, respectively. Their predicted PPB values were relatively close to the literature data. The proposed technique confirmed that lipophilicity, together with acidity significantly influences the PPB of antipsychotics. The described procedure can be regarded as an additional in vitro approach to the modeling of the investigated group of drugs.
Jadranka Odovic, Jovana Trbojevic, Jasna Trbojevic-Stankovic, Dejan Nesic, and Ratomir Jelic
National Library of Serbia
In this study we investigated the relationship between the calcium channel blockers (CCBs), amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem, and their calculated molecular descriptors: polar surface area (PSA), molecular weight (Mw), volume value (Vol), aqueous solubility data (logS), lipophilicity (logP), acidity (pKa values) and plasma protein binding (PPB) data, obtained from relevant literature. The relationships between the computed molecular properties of selected CCBs and their PPB data were investigated by simple linear regression analysis that revealed very low correlations (R2<0.35). When multiple linear regression (MLR) analysis was applied to investigate reliable correlations between the CCBs? calculated molecular descriptors and PPB data, the best correlations were found for the relationships between CCBs, and PPB data and lipophilicity, and with application of the molecular descriptor (Mw, Vol, or pKa) data as additional independent variables (R2=0.623; R2=0.741; R2=0.657, respectively), with an acceptable probability value (P<0.05), confirming that lipophilicity, together with other molecular properties, are essential for the drugs? PPB. We conclude that this could be considered as an additional in vitro approach for modeling CCBs.
Marija S. Jeremić, Hubert Wadepohl, Vesna V. Kojić, Dimitar S. Jakimov, Ratomir Jelić, Suzana Popović, Zoran D. Matović, and Peter Comba
Royal Society of Chemistry (RSC)
Two new Rh(iii)–ed3a complexes [Rh(ed3a)(OH2)]·H2O and Na[Rh(ed3a)Cl]·H2O have shown good antitumor activity, especially against HeLa cell line.
Nevenka Cakić, Tatjana Ž. Verbić, Ratomir M. Jelić, Carlos Platas-Iglesias, and Goran Angelovski
Royal Society of Chemistry (RSC)
Three bismacrocyclic amide derivatives bearing two types of chelating moieties were prepared. The properties of their lanthanide complexes in the absence and presence of calcium, magnesium or zinc ions were studied.
Jovana Trbojevic, Jadranka Odovic, Jasna Trbojevic-Stankovic, Dejan Nesic, and Ratomir Jelic
National Library of Serbia
In the present study, we investigated the relationships between several molecular properties and bioavailability data for seven of the most commonly prescribed angiotensin II receptor antagonists (also known as angiotensin II receptor blockers (ARBs) or sartans), candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan and valsartan. The molecular descriptors of ARBs are:, aqueous solubility (logS values), polar surface area (PSA), molecular weight (Mw), volume value (Vol), lipophilicity (logP values) and the acidity descriptor (pKa1). The respective descriptors were calculated using four different software packages. The relevant bioavailability data were obtained from literature. Among calculated molecular descriptors, simple linear regression analysis showed the best correlation between bioavailability data and the lipophilicity descriptor, logP (R2 = 0.568). Multiple linear regression established good correlations between bioavailability and the lipophilicity descriptor, logP, using the molecular weight, Mw, or the acidity descriptor, pKa1, as an additional, independent variable (with R2 0.661 and 0.682, respectively). Finally, excluding candesartan from the calculations resulted in a very good correlation (R2 = 0.852) between the remaining ARB bioavailability and molecular descriptors MlogP and Mw as independent variables, determined by multiple linear regression.
Ratomir Jelić, Marina Tomović, Stefan Stojanović, Ljubinka Joksović, Ivan Jakovljević, and Predrag Djurdjević
Springer Science and Business Media LLC
Jasna Trbojevic-Stankovic, Jadranka Odovic, Ratomir Jelic, Dejan Nesic, and Biljana Stojimirovic
National Library of Serbia
Calcium channel blockers (CCBs) are among the most widely used drugs in cardiovascular medicine. In this study, nine CCBs (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil and diltiazem) were investigated to assess the relationship between their molecular properties and elimination data obtained from literature. The descriptors of the molecular properties of CCBs were calculated using three software packages. The relationship between computed molecular properties and elimination data collected from relevant literature, initially investigated with simple linear regression analysis, showed poor correlation (R2 <0.25). Application of molecular weight or volume data as additional independent variable, multiple linear regression (MLR) revealed better correlations (R2 ~ 0.38) between CCB renal and fecal elimination data and their lipophilicity. Excluding nimodipine from the calculations resulted in more acceptable correlations. The best correlations were established after computed lipophilicity descriptor and molecular weight were applied (R2 = 0.66 with acceptable probability value).