Suzana Jovanović-Šanta | University of Novi Sad, Faculty of Sciences (original) (raw)

Papers by Suzana Jovanović-Šanta

Zbornik radova / XXVII savetovanje o biotehnologiji sa međunarodnim učešćem, 2022

The effect of cholic acid (CA) dissolved in two different media, namely Hogland nutrient solution... more The effect of cholic acid (CA) dissolved in two different media, namely Hogland nutrient solution and distilled water, on the oxidative stress of maize (Zea mays, L.) and sunflower (Helianthus annuus, L.) was assessed by measuring the intensity of lipid peroxidation. The aim of this screening is to observe possible differences in the results obtained from plants treated with an aqueous solution of cholic acid and those treated with a solution of cholic acid in Hogland's solution. Oxidative stress was assessed on the basis of the estimated intensity of lipid peroxidation (LP), and on the basis of the measured amount of the resulting LP final product, malondialdehyde (MDA). The results showed faster production of MDA in plants treated with cholic acid in Hogland's solution, which indicates that nutrients affect the action of CA.

An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Journal of Ethnopharmacology, 2021

ETHNOPHARMACOLOGICAL RELEVANCE Bile traditionally was used in wound healing, having erodent, anti... more ETHNOPHARMACOLOGICAL RELEVANCE Bile traditionally was used in wound healing, having erodent, antioxidant and antimicrobial potential. Acinetobacter baumannii is a frequent etiological agent of wound infections, exhibiting high level of resistance to conventional antibiotics. AIM OF THE STUDY To determine the effect of selected bile acid sodium salts and their 3-dehydro (i.e. 3-oxo) derivatives, as well as their combinations with commercial antibiotics against A. baumanniia, to confirm bile ethnopharmacological application in wound healing from aspect of microbiology. MATERIALS AND METHODS The sensitivity of reference and multidrug resistant (MDR) A. baumannii strains to bile salts, their derivatives and conventional antibiotics were examined by a microtiter plate method. The interaction of bile salts/derivatives and antibiotics was examined by a checkerboard method and time kill curve method. The interaction of bile salts with ciprofloxacin in terms of micelles formation was examined by DOSY NMR technique. RESULTS The bile salts sodium deoxycholate (Na-DCA) and sodium chenodeoxycholate (Na-CDCA), as well as their derivatives sodium 3-dehydro-deoxycholate (Na-3DH-DCA) and sodium 3-dehydro-chenodeoxycholate (Na-3DH-CDCA), potentiate antibiotic activity and resensitise A. baumannii. The bile salts and their derivatives enhance A. baumannii sensitivity to antibiotics, particularly those that should penetrate cell to exhibit activity. The sodium salts of bile acid derivatives, namely Na-3DH-DCA and Na-3DH-CDCA, showed synergy against both reference and MDR strain in combination with ciprofloxacin or gentamicin, while synergy with gentamicin was obtained in all combinations, regardless of bile salt type and bacterial strains. The synergy with Na-3DH-CDCA was further confirmed by the time-kill curve method, as bacterial number decreased after 12h. NMR experiment revealed that this bile salt derivative and ciprofloxacin form co-aggregates when bile salts concentration was higher than critical micelle concentrations (CMC), which indicate the possibility that bile salts enhance ciprofloxacin cell penetration by membrane destabilization, contributing to the synergy. CONCLUSION The synergistic interactions between bile salts or derivatives with ciprofloxacin and particularly gentamicin represent a promising strategy for the treatment of A. baumannii wound infections.

The objective of this research was to identify bacterial spot-causing pathogen and bacterial anta... more The objective of this research was to identify bacterial spot-causing pathogen and bacterial antagonists for management of the disease using biocontrol agents as environmentally friendly alternatives. Isolates of Bacillus spp. were obtained from the soil samples collected at different localities in Serbia. Antibacterial activity of natural antagonists toward the pathogen isolated from infected pepper leaves was examined using a modified well-diffusion assay and standard germination test. Our results confirmed the presence of Xanthomonas euvesicatoria as the causal agent of bacterial spot of pepper. Screening of 32 Bacillus spp. isolates for antibacterial activity showed that 8 isolates inhibit growth of examined X. euvesicatoria isolates. Four isolates identified as Bacillus subtilis exhibited the highest antibacterial activity by in vitro test (from 5 to 14 mm inhibition zone of bacterial growth). The isolates positively influenced germination of pepper seeds, causing up to 16% and...

The Journal of Steroid Biochemistry and Molecular Biology, 2021

D-ring-fused and D-homo lactone compounds in estratriene and androstane series were synthesized u... more D-ring-fused and D-homo lactone compounds in estratriene and androstane series were synthesized using microwave-assisted reaction conditions. Microwave-irradiated synthesis methods were convenient and effective, and provided high yields with short reaction times. Their inhibition of C17,20-lyase and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) activities were studied in in vitro enzyme assays. D-ring-fused triazolyl estrone analog 24 showed potent inhibition of NADH-complexed 17β-HSD1, with a binding affinity similar to that of the substrate estrone; its inhibition against NADPH-complexed 17β-HSD1 was markedly weaker. Compound 24 also significantly and selectively reduced proliferation of cancer cell lines of gynecological origin. This estrane triazole changed the cell cycle and induced apoptosis of HeLa, SiHa, and MDA-MB-231 cancer cells, measured by both increased subG1 fraction of cells and activation of caspase-independent signaling pathways. A third mode of anti-estrogenic action of 24 saw increased mRNA expression of the SULT1E1 gene in HeLa cells; in contrast, its 3-benzyloxy analog 23 increased mRNA expression of the HSD17B2 gene, thus showing pronounced pro-drug anti-estrogenic activity. Estradiol-derived D-ring triazole compound 24 thus acts at the enzyme, gene expression and cellular levels to decrease the production of active estrogen hormones, demonstrating its pharmacological potential.

Journal of Liquid Chromatography & Related Technologies, 2019

Journal of Molecular Structure, 2019

Sulfonates express a variety of biological and pharmacological activities, which indicates them a... more Sulfonates express a variety of biological and pharmacological activities, which indicates them as compounds of interest, in both synthetic and biological research areas. Among sulfonates, mesylates (methanesulfonyloxy compounds) draw attention by their physicochemical and biological properties, as well as by their reactivity. Here we present X-ray and computational study of 3β-acetoxy-17-methanesulfonyloxy-16,17-secoandrost-5-ene-16-nitrile (1) and its antiproliferative activity against five common human cancer cell lines. Computational study includes geometry optimization, frontier molecular orbital analysis and molecular electrostatic potential mapping at the PW6B95-D3BJ/Def2-TZVP level of theory. Studied mesylate compound 1 expressed quite strong selective anti-proliferative effect against human breast and prostate cancer cell lines. Anticancer activity of this compound was compared to its 17methyl analogs (compounds 2 and 3). Computational study of D-secoandrostane compounds 1-3 allowed us to presume the structural features, important for their chemical reactivity. The differences between the antiproliferative activity of D-secomesylate compound 1 and its 17-methyl analogs 2 and 3 could be explained by possible mechanism in the cancer cells.

Current Organic Chemistry, 2019

: The first attempts at microwave-assisted (MW) syntheses of bile acid derivatives were performed... more : The first attempts at microwave-assisted (MW) syntheses of bile acid derivatives were performed in domestic MW appliances. However, the reproducibility of these syntheses, which were performed in uncontrolled conditions, was very low. In the first part of this overview, compounds synthesized under such conditions are presented. Consequently, with the development of MW technology, MW-assisted reactions in MW reactors became reproducible. Thus, in the second part of this review, syntheses of bile acidsbased compounds in MW reactors are presented. Among others, publications dealing with the following topics will be covered: : − Chemical transformations of hydroxyl and/or carboxyl functions of bile acids into esters or amides, : − Hydroxyl group oxidations, : − Derivatization of oxo-compounds with different nitrogen-containing compounds (e.g. 4-amino-3- substituted-1H-1,2,4-triazole-5-thiones, thiocarbohydrazides and thiosemicarbazides) : Bile acid-based molecular tweezers, capable of stereospecific molecular recognition : Reactions of hydroxyl functions to give chlorine derivatives, presenting reactive intermediates in substitution reactions with N- or O-containing nucleophilic arylhydrazides, urea derivatives, substituted thiadiazoles or triazoles or amino acid methyl esters, mainly in solvent-free conditions. : Some of the synthesized compounds expressed antimicrobial potential and/or good recognition properties as artificial receptors for specific amino acids or anions. : Detailed comparisons between conventional and MW-assisted procedures for chemical transformations of bile acids are given in most of the presented publications. Based on these results, MW irradiation methods are simpler, more efficient, cleaner and faster than conventional synthetic methods, meeting the requirements of green chemistry.

RSC Advances, 2016

Five different salicylate based ionic liquids were prepared in order to study their toxicity. Aqu... more Five different salicylate based ionic liquids were prepared in order to study their toxicity. Aquatic organisms (A. salina) and a human non-tumor cell line (normal fetal lung fibroblasts, MRC-5) were used for that purpose.

Bioorganic & Medicinal Chemistry, 2015

Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic pote... more Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene androstane derivatives. The antiproliferative impact was examined on six human tumor cell lines, including two types of breast (MCF-7 and MDA-MB-231), prostate (PC3), cervical (HeLa), colon (HT 29) and lung cancer (A549), as well as one normal fetal lung fibroblasts cell line (MRC-5). All derivatives selectively decreased proliferation of estrogen receptor negative MDA-MB-231 breast cancer cells after 48h and 72h treatment and compounds showed time-dependent activity. We used this cell line to investigate cell cycle modulation and apoptotic cell death induction by flow cytometry, expression of apoptotic proteins by Western blot and apoptotic morphology by visual observation. Tested androstane derivatives affected the cell cycle distribution and induced apoptosis and necrosis. Compounds had different and specific mode of action, depending on derivative type and exposure time. Some compounds induced significant apoptosis measured by Annexin V test compared to reference compound formestane. Higher expression of pro-apoptotic BAX, downregulation of anti-apoptotic Bcl-2 and cleavage of PARP protein were confirmed in almost all treated samples, but the lack of caspase-3 activation suggested the induction of apoptosis in caspase-independent manner. More cells with apoptotic morphology were observed in samples after prolonged treatment. Structure-activity relationship analysis was performed to find correlations between the structure variations of investigated derivatives and observed biological effects. Results of this study showed that some of the investigated androstane derivatives have good biomedical potential and could be candidates for anticancer drug development.

Collection of Czechoslovak Chemical Communications, 2006

Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with ... more Since many of newly synthesised D-secoestratriene derivatives showed antiestrogenic effect, with almost a total loss of estrogenic activity, we studied the effects of some of these compounds on estrogen receptors (ER), the translocation of the estrogen-ER complexes formed in presence of competing substances into the nucleus, as well as the binding of these complexes to DNA. The results of uterotrophic effects of analysed derivatives are in agreement with the influence of these compounds on activity and binding parameters of estrogen receptors. Namely, compounds that show relatively high antiestrogenic activity predominantly increaseKdand inhibit translocation to nuclei of radioactive complexes formed in their presence. On the other hand, compounds that do not significantly change binding parameters of estrogen receptors do not show antiestrogenic effect inin vivoexperiments.

Book of Proceedings: 1st International Conference on Chemo and BioInformatics, 2021

Our in vitro studies showed that a couple of perspective steroidal derivatives showed previously ... more Our in vitro studies showed that a couple of perspective steroidal derivatives showed previously biomedical potential via enzyme inhibition, receptor binding or antiproliferative effect against the cancer cells of reproductive tissues are able to bind to human CYP7 enzymes – key enzymes taking part in hydroxylation of cholesterol, 25-, 27-hydroxycholesterol and a number of steroidal hormones. In silico screening of binding affinity of the modified steroids toward CYP7 enzymes showed that interaction energy for the new ligands is comparable with consequent values, calculated for the ‘essential’ substrates of the enzymes – cholestenone (CYP7A1) and DHEA (CYP7B1). However, no correlation between binding energy and the affinity of the ligand was found. Novel ligands interact with conserved amino acids taking part in stabilization of natural substrates of CYP7 enzymes. A couple of structural features, governing ligand binding, were identified. Among which are planar structure of A-ring f...

Journal of the Serbian Chemical Society

Ionic liquids (ILs) are well known for their physicochemical properties that recommend them for m... more Ionic liquids (ILs) are well known for their physicochemical properties that recommend them for many purposes. However, many ILs are not environmentally friendly. Bearing these facts in mind, a series of imidazoliumand salicylate-based ILs with low general toxicity were designed and their pharmacological potential studied. Herein, their antiproliferative effect against human cancer cell lines and antimicrobial activity on selected Gram-positive and Gram-negative bacteria and Candida strains are presented. ILs with 1-butyl- -3-methylimidazolium or imidazolium cation (IL 1 and compound 5), with the lowest dipole moments and highest lipophilicity, exerted highest cytotoxicity against colon and/or lung cancer cells, manifesting high selectivity to the normal cells. The most non-polar IL with the 1-butyl-3-methylimidazolium cation expressed the strongest anticancer potential, but it was also toxic against normal cells, although its cytotoxicity was less than the cytotoxic effect of comme...

The Journal of Steroid Biochemistry and Molecular Biology

Cytochromes P450 are key enzymes for steroid hormone biosynthesis in human body. They are conside... more Cytochromes P450 are key enzymes for steroid hormone biosynthesis in human body. They are considered as targets for the screening of novel high efficient drugs. The results of screening of bile acids and androstane derivatives toward human recombinant steroid 17α-hydroxylase/17,20-lyase (CYP17A1) are presented in this paper. A group of steroids, binding with micromolar or submicromolar affinity (in a range from 9 µM - less than 0.1 µM), was identified. Results presented here showed that these steroidal compounds are able to decrease rate of hydroxylation of essential CYP17A1 substrate - progesterone, while some compounds completely inhibited enzyme activity. Structure-activity relationship (SAR) analysis based on in vitro and in silico studies showed that high affinity of the enzyme to bile acids derivatives is correlated with side chain hydrophobicity and presence of hydroxyl or keto group at C3 position. From the other side, bile acid-derived compounds with more polar side chain or substituents at C7 and C12 positions possess higher Kd values. Among androstane-derived steroids couple of Δ5-steroids with hydroxyl group at C3 position, as well as 16,17-secosteroids, were found to be high affinity ligands of this enzyme. The data obtained could be useful for the design of novel highly efficient inhibitors of CYP17A1, since the bile acids-derived compounds are for first time recognized as effective CYP17A1 inhibitors.

Starting from 3-benzyloxy-17-hydroxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile (>), 17-tosylate... more Starting from 3-benzyloxy-17-hydroxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile (>), 17-tosylate > and also 17-chloro-, 17-bromo-and 17-iodo-derivatives 4b, 5b, and 6b, were obtained. The fluoro-derivative !> was obtained from > in the reaction with tetrabutyl ammonium fluoride. The deprotection of the 3-hydroxyl group was achieved by action of hydrogen in presence of Pd/C as a catalyst, yielding six new 3-hydroxy-16,17-seco-estrone derivatives.

Materials Science Forum, 2000