TY  - JOUR
AU  - Pavić, Aleksandar
AU  - Stojanović, Zoran
AU  - Pekmezović, Marina
AU  - Veljović, Đorđe
AU  - O'Connor, Kevin
AU  - Malagurski, Ivana
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1554
AB  - Immobilizing antifungal polyenes such as nystatin (Nys) and amphotericin B (AmB) into biodegradable formulations is advantageous compared to free drug administration providing sustained release, reduced dosing due to localized targeting and overall reduced systemic drug toxicity. In this study, we encapsulated Nys and AmB in medium chain length polyhydroxyalkanoates (mcl-PHA) microspheres (7-8 mu m in diameter). The obtained formulations have been validated for antifungal activity in vitro against a panel of pathogenic fungi including species of Candida, Aspergillus, Microsporum and Trichophyton genera and toxicity and efficacy in vivo using the zebrafish model of disseminated candidiasis. While free polyenes, especially AmB, were highly toxic to zebrafish embryos at the effective (MIC) doses, after their loading into mcl-PHA microspheres, inner organ toxicity and teratogenicity associated with both drugs were not observed, even at 100 x MIC doses. The obtained mcl-PHA/polyene formulations have successfully eradicated C. albicans infection and showed an improved therapeutic profile in zebrafish by enhancing infected embryos survival. This approach is contributing to the antifungal arsenal as polyenes, although the first broad-spectrum antifungals on the market are still the gold standard for treatment of fungal infections.
PB  - MDPI, Basel
T2  - Pharmaceutics
T1  - Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model
IS  - 4
VL  - 14
DO  - 10.3390/pharmaceutics14040696
ER  - 

@article{
author = "Pavić, Aleksandar and Stojanović, Zoran and Pekmezović, Marina and Veljović, Đorđe and O'Connor, Kevin and Malagurski, Ivana and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "Immobilizing antifungal polyenes such as nystatin (Nys) and amphotericin B (AmB) into biodegradable formulations is advantageous compared to free drug administration providing sustained release, reduced dosing due to localized targeting and overall reduced systemic drug toxicity. In this study, we encapsulated Nys and AmB in medium chain length polyhydroxyalkanoates (mcl-PHA) microspheres (7-8 mu m in diameter). The obtained formulations have been validated for antifungal activity in vitro against a panel of pathogenic fungi including species of Candida, Aspergillus, Microsporum and Trichophyton genera and toxicity and efficacy in vivo using the zebrafish model of disseminated candidiasis. While free polyenes, especially AmB, were highly toxic to zebrafish embryos at the effective (MIC) doses, after their loading into mcl-PHA microspheres, inner organ toxicity and teratogenicity associated with both drugs were not observed, even at 100 x MIC doses. The obtained mcl-PHA/polyene formulations have successfully eradicated C. albicans infection and showed an improved therapeutic profile in zebrafish by enhancing infected embryos survival. This approach is contributing to the antifungal arsenal as polyenes, although the first broad-spectrum antifungals on the market are still the gold standard for treatment of fungal infections.",
publisher = "MDPI, Basel",
journal = "Pharmaceutics",
title = "Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model",
number = "4",
volume = "14",
doi = "10.3390/pharmaceutics14040696"
}

Pavić, A., Stojanović, Z., Pekmezović, M., Veljović, Đ., O'Connor, K., Malagurski, I.,& Nikodinović-Runić, J.. (2022). Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model. in Pharmaceutics
MDPI, Basel., 14(4).
https://doi.org/10.3390/pharmaceutics14040696

Pavić A, Stojanović Z, Pekmezović M, Veljović Đ, O'Connor K, Malagurski I, Nikodinović-Runić J. Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model. in Pharmaceutics. 2022;14(4).
doi:10.3390/pharmaceutics14040696 .

Pavić, Aleksandar, Stojanović, Zoran, Pekmezović, Marina, Veljović, Đorđe, O'Connor, Kevin, Malagurski, Ivana, Nikodinović-Runić, Jasmina, "Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model" in Pharmaceutics, 14, no. 4 (2022),
https://doi.org/10.3390/pharmaceutics14040696 . .

TY  - JOUR
AU  - Lazić, Jelena
AU  - Ajdačić, Vladimir
AU  - Vojnović, Sandra
AU  - Zlatović, Mario
AU  - Pekmezović, Marina
AU  - Mogavero, Selene
AU  - Opsenica, Igor
AU  - Nikodinović-Runić, Jasmina
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1195
AB  - Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.
PB  - Springer, New York
T2  - Applied Microbiology and Biotechnology
T1  - Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction
EP  - 1901
IS  - 4
SP  - 1889
VL  - 102
DO  - 10.1007/s00253-018-8749-3
ER  - 

@article{
author = "Lazić, Jelena and Ajdačić, Vladimir and Vojnović, Sandra and Zlatović, Mario and Pekmezović, Marina and Mogavero, Selene and Opsenica, Igor and Nikodinović-Runić, Jasmina",
year = "2018",
abstract = "Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.",
publisher = "Springer, New York",
journal = "Applied Microbiology and Biotechnology",
title = "Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction",
pages = "1901-1889",
number = "4",
volume = "102",
doi = "10.1007/s00253-018-8749-3"
}

Lazić, J., Ajdačić, V., Vojnović, S., Zlatović, M., Pekmezović, M., Mogavero, S., Opsenica, I.,& Nikodinović-Runić, J.. (2018). Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. in Applied Microbiology and Biotechnology
Springer, New York., 102(4), 1889-1901.
https://doi.org/10.1007/s00253-018-8749-3

Lazić J, Ajdačić V, Vojnović S, Zlatović M, Pekmezović M, Mogavero S, Opsenica I, Nikodinović-Runić J. Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. in Applied Microbiology and Biotechnology. 2018;102(4):1889-1901.
doi:10.1007/s00253-018-8749-3 .

Lazić, Jelena, Ajdačić, Vladimir, Vojnović, Sandra, Zlatović, Mario, Pekmezović, Marina, Mogavero, Selene, Opsenica, Igor, Nikodinović-Runić, Jasmina, "Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction" in Applied Microbiology and Biotechnology, 102, no. 4 (2018):1889-1901,
https://doi.org/10.1007/s00253-018-8749-3 . .

TY  - JOUR
AU  - Savić, Nada D.
AU  - Vojnović, Sandra
AU  - Glišić, Biljana
AU  - Crochet, Aurelien
AU  - Pavić, Aleksandar
AU  - Janjić, Goran V.
AU  - Pekmezović, Marina
AU  - Opsenica, Igor M.
AU  - Fromm, Katharina M.
AU  - Nikodinović-Runić, Jasmina
AU  - Djuran, Milos
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1098
AB  - Mononuclear silver(I) complexes with 1,7-phenanthroline (1,7-phen), [Ag(NO3-O,O') (1,7-phen-N7)(2)] (1) and [Ag(1,7-phen-N7)(2)]X, X = ClO4- (2), CF3SO3- (3), BF4- (4) and SbF6- (5) were synthesized and structurally characterized by NMR (H-1 and C-13), IR and UV-Vis spectroscopy and ESI mass spectrometry. The crystal structures of 1, 3 and 4 were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,7-phen coordinates to the Ag(I) ion in a monodentate fashion via the less sterically hindered N7 nitrogen atom. The investigation of the solution stability of 1-5 in DMSO revealed that they are sufficiently stable in this solvent at room temperature. Complexes 1-5 showed selectivity towards Candida spp. in comparison to bacteria, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MIC) between 1.2 and 11.3 mu M. Based on the lowest MIC values and the lowest cytotoxicity against healthy human fibroblasts with selectivity index of more than 30, the antifungal potential was examined in detail for the complex 1. It had the ability to attenuate C. albicans virulence and to reduce epithelial cell damage in the cell infection model. Induction of reactive oxygen species (ROS) response has been detected in C. albicans, with fungal DNA being one of the possible target biomolecules. The toxicity profile of 1 in the zebrafish model (Danio rerio) revealed improved safety and activity in comparison to that of clinically utilized silver(I) sulfadiazine.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth
EP  - 773
SP  - 760
VL  - 156
DO  - 10.1016/j.ejmech.2018.07.049
ER  - 

@article{
author = "Savić, Nada D. and Vojnović, Sandra and Glišić, Biljana and Crochet, Aurelien and Pavić, Aleksandar and Janjić, Goran V. and Pekmezović, Marina and Opsenica, Igor M. and Fromm, Katharina M. and Nikodinović-Runić, Jasmina and Djuran, Milos",
year = "2018",
abstract = "Mononuclear silver(I) complexes with 1,7-phenanthroline (1,7-phen), [Ag(NO3-O,O') (1,7-phen-N7)(2)] (1) and [Ag(1,7-phen-N7)(2)]X, X = ClO4- (2), CF3SO3- (3), BF4- (4) and SbF6- (5) were synthesized and structurally characterized by NMR (H-1 and C-13), IR and UV-Vis spectroscopy and ESI mass spectrometry. The crystal structures of 1, 3 and 4 were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,7-phen coordinates to the Ag(I) ion in a monodentate fashion via the less sterically hindered N7 nitrogen atom. The investigation of the solution stability of 1-5 in DMSO revealed that they are sufficiently stable in this solvent at room temperature. Complexes 1-5 showed selectivity towards Candida spp. in comparison to bacteria, effectively inhibiting the growth of four different Candida species with minimal inhibitory concentrations (MIC) between 1.2 and 11.3 mu M. Based on the lowest MIC values and the lowest cytotoxicity against healthy human fibroblasts with selectivity index of more than 30, the antifungal potential was examined in detail for the complex 1. It had the ability to attenuate C. albicans virulence and to reduce epithelial cell damage in the cell infection model. Induction of reactive oxygen species (ROS) response has been detected in C. albicans, with fungal DNA being one of the possible target biomolecules. The toxicity profile of 1 in the zebrafish model (Danio rerio) revealed improved safety and activity in comparison to that of clinically utilized silver(I) sulfadiazine.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth",
pages = "773-760",
volume = "156",
doi = "10.1016/j.ejmech.2018.07.049"
}

Savić, N. D., Vojnović, S., Glišić, B., Crochet, A., Pavić, A., Janjić, G. V., Pekmezović, M., Opsenica, I. M., Fromm, K. M., Nikodinović-Runić, J.,& Djuran, M.. (2018). Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 156, 760-773.
https://doi.org/10.1016/j.ejmech.2018.07.049

Savić ND, Vojnović S, Glišić B, Crochet A, Pavić A, Janjić GV, Pekmezović M, Opsenica IM, Fromm KM, Nikodinović-Runić J, Djuran M. Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth. in European Journal of Medicinal Chemistry. 2018;156:760-773.
doi:10.1016/j.ejmech.2018.07.049 .

Savić, Nada D., Vojnović, Sandra, Glišić, Biljana, Crochet, Aurelien, Pavić, Aleksandar, Janjić, Goran V., Pekmezović, Marina, Opsenica, Igor M., Fromm, Katharina M., Nikodinović-Runić, Jasmina, Djuran, Milos, "Mononuclear silver(I) complexes with 1,7-phenanthroline as potent inhibitors of Candida growth" in European Journal of Medicinal Chemistry, 156 (2018):760-773,
https://doi.org/10.1016/j.ejmech.2018.07.049 . .

TY  - JOUR
AU  - Simić, Milena
AU  - Paunović, Nikola
AU  - Borić, Ivan
AU  - Randjelović, Jelena
AU  - Vojnović, Sandra
AU  - Nikodinović-Runić, Jasmina
AU  - Pekmezović, Marina
AU  - Savić, Vladimir
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/971
AB  - A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & Medicinal Chemistry Letters
T1  - Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies
EP  - 239
IS  - 1
SP  - 235
VL  - 26
DO  - 10.1016/j.bmcl.2015.08.086
ER  - 

@article{
author = "Simić, Milena and Paunović, Nikola and Borić, Ivan and Randjelović, Jelena and Vojnović, Sandra and Nikodinović-Runić, Jasmina and Pekmezović, Marina and Savić, Vladimir",
year = "2016",
abstract = "A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & Medicinal Chemistry Letters",
title = "Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies",
pages = "239-235",
number = "1",
volume = "26",
doi = "10.1016/j.bmcl.2015.08.086"
}

Simić, M., Paunović, N., Borić, I., Randjelović, J., Vojnović, S., Nikodinović-Runić, J., Pekmezović, M.,& Savić, V.. (2016). Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies. in Bioorganic & Medicinal Chemistry Letters
Pergamon-Elsevier Science Ltd, Oxford., 26(1), 235-239.
https://doi.org/10.1016/j.bmcl.2015.08.086

Simić M, Paunović N, Borić I, Randjelović J, Vojnović S, Nikodinović-Runić J, Pekmezović M, Savić V. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies. in Bioorganic & Medicinal Chemistry Letters. 2016;26(1):235-239.
doi:10.1016/j.bmcl.2015.08.086 .

Simić, Milena, Paunović, Nikola, Borić, Ivan, Randjelović, Jelena, Vojnović, Sandra, Nikodinović-Runić, Jasmina, Pekmezović, Marina, Savić, Vladimir, "Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies" in Bioorganic & Medicinal Chemistry Letters, 26, no. 1 (2016):235-239,
https://doi.org/10.1016/j.bmcl.2015.08.086 . .

TY  - JOUR
AU  - Ajdačić, Vladimir
AU  - Šenerović, Lidija
AU  - Vranić, Marija
AU  - Pekmezović, Marina
AU  - Arsić-Arsenijević, Valentina
AU  - Veselinović, Aleksandar
AU  - Veselinović, Jovana
AU  - Solaja, Bogdan A.
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor M.
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/991
AB  - A series of new thiophene-based guanylhydrazones (iminoguanidines) were synthesized in high yields using a straightforward two-step procedure. The antifungal activity of compounds was evaluated against a wide range of medicaly important fungal strains including yeasts, molds, and dermatophytes in comparison to clinically used drug voriconazole. Cytotoxic properties of compounds were also determined using human lung fibroblast cell line and hemolysis assay. All guanylhydrazones showed significant activity against broad spectrum of clinically important species of Candida spp., Aspergillus fumigatus, Fusarium oxysporum, Microsporum canis and Trichophyton mentagrophytes, which was in some cases comparable or better than activity of voriconazole. More importantly, compounds 10, 11, 13, 14, 18 and 21 exhibited excellent activity against voriconazole-resistant Candida albicans CA5 with very low minimal inhibitory concentration (MIC) values  lt 2 mu g mL(-1). Derivative 14, bearing bromine on the phenyl ring, was the most effective compound with MICs ranging from 0.25 to 6.25 g mL(-1). However, bis-guanylhydrazone 18 showed better selectivity in terms of therapeutic index values. In vivo embryotoxicity on zebrafish (Danio rerio) showed improved toxicity profile of 11, 14 and 18 in comparison to that of voriconazole. Most guanylhydrazones also inhibited C albicans yeast to hyphal transition, essential for its biofilm formation, while 11 and 18 were able to disperse preformed Candida biofilms. All guanylhydrazones showed the equal potential to interact with genomic DNA of C albicans in vitro, thus indicating a possible mechanism of their action, as well as possible mechanism of observed cytotoxic effects. Tested compounds did not have significant hemolytic effect and caused low liposome leakage, which excluded the cell membrane as a primary target. On the basis of computational docking experiments using both human and cytochrome P450 from Candida it was concluded that the most active guanylhydrazones had minimal structural prerequisites to interact with the cytochrome P450 14a-demethylase (CYP51). Promising guanylhydrazone derivatives also showed satisfactory pharmacokinetic profile based on molecular calculations.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & Medicinal Chemistry
T1  - Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates
EP  - 1291
IS  - 6
SP  - 1277
VL  - 24
DO  - 10.1016/j.bmc.2016.01.058
ER  - 

@article{
author = "Ajdačić, Vladimir and Šenerović, Lidija and Vranić, Marija and Pekmezović, Marina and Arsić-Arsenijević, Valentina and Veselinović, Aleksandar and Veselinović, Jovana and Solaja, Bogdan A. and Nikodinović-Runić, Jasmina and Opsenica, Igor M.",
year = "2016",
abstract = "A series of new thiophene-based guanylhydrazones (iminoguanidines) were synthesized in high yields using a straightforward two-step procedure. The antifungal activity of compounds was evaluated against a wide range of medicaly important fungal strains including yeasts, molds, and dermatophytes in comparison to clinically used drug voriconazole. Cytotoxic properties of compounds were also determined using human lung fibroblast cell line and hemolysis assay. All guanylhydrazones showed significant activity against broad spectrum of clinically important species of Candida spp., Aspergillus fumigatus, Fusarium oxysporum, Microsporum canis and Trichophyton mentagrophytes, which was in some cases comparable or better than activity of voriconazole. More importantly, compounds 10, 11, 13, 14, 18 and 21 exhibited excellent activity against voriconazole-resistant Candida albicans CA5 with very low minimal inhibitory concentration (MIC) values  lt 2 mu g mL(-1). Derivative 14, bearing bromine on the phenyl ring, was the most effective compound with MICs ranging from 0.25 to 6.25 g mL(-1). However, bis-guanylhydrazone 18 showed better selectivity in terms of therapeutic index values. In vivo embryotoxicity on zebrafish (Danio rerio) showed improved toxicity profile of 11, 14 and 18 in comparison to that of voriconazole. Most guanylhydrazones also inhibited C albicans yeast to hyphal transition, essential for its biofilm formation, while 11 and 18 were able to disperse preformed Candida biofilms. All guanylhydrazones showed the equal potential to interact with genomic DNA of C albicans in vitro, thus indicating a possible mechanism of their action, as well as possible mechanism of observed cytotoxic effects. Tested compounds did not have significant hemolytic effect and caused low liposome leakage, which excluded the cell membrane as a primary target. On the basis of computational docking experiments using both human and cytochrome P450 from Candida it was concluded that the most active guanylhydrazones had minimal structural prerequisites to interact with the cytochrome P450 14a-demethylase (CYP51). Promising guanylhydrazone derivatives also showed satisfactory pharmacokinetic profile based on molecular calculations.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & Medicinal Chemistry",
title = "Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates",
pages = "1291-1277",
number = "6",
volume = "24",
doi = "10.1016/j.bmc.2016.01.058"
}

Ajdačić, V., Šenerović, L., Vranić, M., Pekmezović, M., Arsić-Arsenijević, V., Veselinović, A., Veselinović, J., Solaja, B. A., Nikodinović-Runić, J.,& Opsenica, I. M.. (2016). Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates. in Bioorganic & Medicinal Chemistry
Pergamon-Elsevier Science Ltd, Oxford., 24(6), 1277-1291.
https://doi.org/10.1016/j.bmc.2016.01.058

Ajdačić V, Šenerović L, Vranić M, Pekmezović M, Arsić-Arsenijević V, Veselinović A, Veselinović J, Solaja BA, Nikodinović-Runić J, Opsenica IM. Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates. in Bioorganic & Medicinal Chemistry. 2016;24(6):1277-1291.
doi:10.1016/j.bmc.2016.01.058 .

Ajdačić, Vladimir, Šenerović, Lidija, Vranić, Marija, Pekmezović, Marina, Arsić-Arsenijević, Valentina, Veselinović, Aleksandar, Veselinović, Jovana, Solaja, Bogdan A., Nikodinović-Runić, Jasmina, Opsenica, Igor M., "Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates" in Bioorganic & Medicinal Chemistry, 24, no. 6 (2016):1277-1291,
https://doi.org/10.1016/j.bmc.2016.01.058 . .

TY  - JOUR
AU  - Pekmezović, Marina
AU  - Aleksić, Ivana
AU  - Barac, Aleksandra
AU  - Arsić-Arsenijević, Valentina
AU  - Vasiljević, Branka
AU  - Nikodinović-Runić, Jasmina
AU  - Šenerović, Lidija
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/953
AB  - Mixed microbial infections caused by Pseudomonas aeruginosa and pathogenic fungi are commonly found in patients with chronic infections and constitute a significant health care burden. The aim of this study was to address the potential polymicrobial antibiofilm activity of pompia and grapefruit essential oils (EOs). The mechanism of antimicrobial activity of EOs was analysed. EOs of pompia and grapefruit inhibited fungal growth with MIC concentrations between 50 and 250 mg L-1, whereas no effect on P. aeruginosa growth was observed. Both citrus EOs inhibited formation of bacterial and fungal monomicrobial biofilms in concentrations of 50 mg L-1 and were efficient in potentiating the activity of clinically used antimicrobials in vitro. The concentration of 10 mg L-1 EOs inhibited mixed biofilm formation composed of P. aeruginosa and Aspergillus fumigatus or Scedosporium apiospermum. Citrus EOs affected quorum sensing in P. aeruginosa and caused fast permeabilisation of Candida albicans membrane. Pompia and grapefruit EOs potently inhibited biofilm formation and could be used for the control of common polymicrobial infections.
PB  - Oxford Univ Press, Oxford
T2  - Pathogens and Disease
T1  - Prevention of polymicrobial biofilms composed of Pseudomonas aeruginosa and pathogenic fungi by essential oils from selected Citrus species
IS  - 8
VL  - 74
DO  - 10.1093/femspd/ftw102
ER  - 

@article{
author = "Pekmezović, Marina and Aleksić, Ivana and Barac, Aleksandra and Arsić-Arsenijević, Valentina and Vasiljević, Branka and Nikodinović-Runić, Jasmina and Šenerović, Lidija",
year = "2016",
abstract = "Mixed microbial infections caused by Pseudomonas aeruginosa and pathogenic fungi are commonly found in patients with chronic infections and constitute a significant health care burden. The aim of this study was to address the potential polymicrobial antibiofilm activity of pompia and grapefruit essential oils (EOs). The mechanism of antimicrobial activity of EOs was analysed. EOs of pompia and grapefruit inhibited fungal growth with MIC concentrations between 50 and 250 mg L-1, whereas no effect on P. aeruginosa growth was observed. Both citrus EOs inhibited formation of bacterial and fungal monomicrobial biofilms in concentrations of 50 mg L-1 and were efficient in potentiating the activity of clinically used antimicrobials in vitro. The concentration of 10 mg L-1 EOs inhibited mixed biofilm formation composed of P. aeruginosa and Aspergillus fumigatus or Scedosporium apiospermum. Citrus EOs affected quorum sensing in P. aeruginosa and caused fast permeabilisation of Candida albicans membrane. Pompia and grapefruit EOs potently inhibited biofilm formation and could be used for the control of common polymicrobial infections.",
publisher = "Oxford Univ Press, Oxford",
journal = "Pathogens and Disease",
title = "Prevention of polymicrobial biofilms composed of Pseudomonas aeruginosa and pathogenic fungi by essential oils from selected Citrus species",
number = "8",
volume = "74",
doi = "10.1093/femspd/ftw102"
}

Pekmezović, M., Aleksić, I., Barac, A., Arsić-Arsenijević, V., Vasiljević, B., Nikodinović-Runić, J.,& Šenerović, L.. (2016). Prevention of polymicrobial biofilms composed of Pseudomonas aeruginosa and pathogenic fungi by essential oils from selected Citrus species. in Pathogens and Disease
Oxford Univ Press, Oxford., 74(8).
https://doi.org/10.1093/femspd/ftw102

Pekmezović M, Aleksić I, Barac A, Arsić-Arsenijević V, Vasiljević B, Nikodinović-Runić J, Šenerović L. Prevention of polymicrobial biofilms composed of Pseudomonas aeruginosa and pathogenic fungi by essential oils from selected Citrus species. in Pathogens and Disease. 2016;74(8).
doi:10.1093/femspd/ftw102 .

Pekmezović, Marina, Aleksić, Ivana, Barac, Aleksandra, Arsić-Arsenijević, Valentina, Vasiljević, Branka, Nikodinović-Runić, Jasmina, Šenerović, Lidija, "Prevention of polymicrobial biofilms composed of Pseudomonas aeruginosa and pathogenic fungi by essential oils from selected Citrus species" in Pathogens and Disease, 74, no. 8 (2016),
https://doi.org/10.1093/femspd/ftw102 . .

TY  - JOUR
AU  - Pekmezović, M.
AU  - Rajković, K.
AU  - Barac, A.
AU  - Šenerović, Lidija
AU  - Arsić-Arsenijević, Valentina
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/809
AB  - The antifungal effect of essential oils (EOs) of Thymus vulgaris L. (EOT.vulgaris) and Cinnamomum cassia L. (EOC.cassia) against Aspergillus flavus spores was evaluated by determining minimum inhibitory concentration, minimum fungicidal concentrations and fungicidal kinetics. Kinetic model of fungicidal activity of individual EOT.vulgaris and EOC.cassia was developed and its parameters were used to make EO mixture with optimal ratio of individual EOs. Synergism and speed of fungicidal effect of EO mixtures against A. flavus spores were evaluated. Kinetic model revealed optimal ratio EOT.vulgaris: EOC.cassia as 14:1 in mixture. Observed result was validated by comparing fungicidal effect of this mixture to commonly used ratio 1:1 and intermediate 7:1 EO mixtures. All three mixtures showed partial fungicidal synergism, but the time point of fungicidal effect was different. The fastest fungicidal effect was observed in 14:1 EO mixture (after 90 mm), followed by 7:1 (110 min) and 1:1 (180 min). The difference in the speed of fungicidal effect could not be detected using standard microdilution susceptibility tests, which demonstrated the importance and usefulness of developed kinetic model for further investigations.
PB  - Elsevier Science Bv, Amsterdam
T2  - Biochemical Engineering Journal
T1  - Development of kinetic model for testing antifungal effect of Thymus vulgaris L. and Cinnamomum cassia L. essential oils on Aspergillus flavus spores and application for optimization of synergistic effect
EP  - 137
SP  - 131
VL  - 99
DO  - 10.1016/j.bej.2015.03.024
ER  - 

@article{
author = "Pekmezović, M. and Rajković, K. and Barac, A. and Šenerović, Lidija and Arsić-Arsenijević, Valentina",
year = "2015",
abstract = "The antifungal effect of essential oils (EOs) of Thymus vulgaris L. (EOT.vulgaris) and Cinnamomum cassia L. (EOC.cassia) against Aspergillus flavus spores was evaluated by determining minimum inhibitory concentration, minimum fungicidal concentrations and fungicidal kinetics. Kinetic model of fungicidal activity of individual EOT.vulgaris and EOC.cassia was developed and its parameters were used to make EO mixture with optimal ratio of individual EOs. Synergism and speed of fungicidal effect of EO mixtures against A. flavus spores were evaluated. Kinetic model revealed optimal ratio EOT.vulgaris: EOC.cassia as 14:1 in mixture. Observed result was validated by comparing fungicidal effect of this mixture to commonly used ratio 1:1 and intermediate 7:1 EO mixtures. All three mixtures showed partial fungicidal synergism, but the time point of fungicidal effect was different. The fastest fungicidal effect was observed in 14:1 EO mixture (after 90 mm), followed by 7:1 (110 min) and 1:1 (180 min). The difference in the speed of fungicidal effect could not be detected using standard microdilution susceptibility tests, which demonstrated the importance and usefulness of developed kinetic model for further investigations.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Biochemical Engineering Journal",
title = "Development of kinetic model for testing antifungal effect of Thymus vulgaris L. and Cinnamomum cassia L. essential oils on Aspergillus flavus spores and application for optimization of synergistic effect",
pages = "137-131",
volume = "99",
doi = "10.1016/j.bej.2015.03.024"
}

Pekmezović, M., Rajković, K., Barac, A., Šenerović, L.,& Arsić-Arsenijević, V.. (2015). Development of kinetic model for testing antifungal effect of Thymus vulgaris L. and Cinnamomum cassia L. essential oils on Aspergillus flavus spores and application for optimization of synergistic effect. in Biochemical Engineering Journal
Elsevier Science Bv, Amsterdam., 99, 131-137.
https://doi.org/10.1016/j.bej.2015.03.024

Pekmezović M, Rajković K, Barac A, Šenerović L, Arsić-Arsenijević V. Development of kinetic model for testing antifungal effect of Thymus vulgaris L. and Cinnamomum cassia L. essential oils on Aspergillus flavus spores and application for optimization of synergistic effect. in Biochemical Engineering Journal. 2015;99:131-137.
doi:10.1016/j.bej.2015.03.024 .

Pekmezović, M., Rajković, K., Barac, A., Šenerović, Lidija, Arsić-Arsenijević, Valentina, "Development of kinetic model for testing antifungal effect of Thymus vulgaris L. and Cinnamomum cassia L. essential oils on Aspergillus flavus spores and application for optimization of synergistic effect" in Biochemical Engineering Journal, 99 (2015):131-137,
https://doi.org/10.1016/j.bej.2015.03.024 . .

TY  - JOUR
AU  - Milisavljević, Mira
AU  - Zivković, S.
AU  - Pekmezović, M.
AU  - Stanković, Nada
AU  - Vojnović, Sandra
AU  - Vasiljević, Branka
AU  - Šenerović, Lidija
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/876
AB  - AimsThe aim of this study was to address the toxicity of recently described polyene macrolide 32, 33-didehydroroflamycoin (DDHR) on a wide range of fungal pathogens and its potential to control plant fungal diseases. Methods and ResultsThe antifungal activity of DDHR invitro was examined against common human and plant pathogenic fungi using a broth microdilution assay and a disk diffusion assay. Minimum inhibitory concentrations ranged from 125 to 35gml(-1). A radial growth inhibition assay showed that DDHR inhibited mycelia growth, inducing mycelial necrosis and affecting sporulation. During the invivo assay on apple fruits administration of DDHR 1h before fungal inoculation inhibited spreading of the infection. Importantly, DDHR exhibited no phytotoxic effects on the model plant, Capsicum annum, verified by the plant growth rate and chlorophyll content. ConclusionsDDHR inhibits growth of various plant pathogens invitro with the strongest activity against Alternaria alternata, Colletotrichum acutatum and Penicillium expansum, and protects apple fruits from decay. Significance and Impact of the StudyThis is the first report of the inhibitory effect of DDHR on important pathogenic fungal isolates. DDHR could be a good scaffold for developing new antifungal agents for fruit and vegetable protection.
PB  - Wiley, Hoboken
T2  - Journal of Applied Microbiology
T1  - Control of human and plant fungal pathogens using pentaene macrolide 32, 33-didehydroroflamycoin
EP  - 1434
IS  - 6
SP  - 1426
VL  - 118
DO  - 10.1111/jam.12811
ER  - 

@article{
author = "Milisavljević, Mira and Zivković, S. and Pekmezović, M. and Stanković, Nada and Vojnović, Sandra and Vasiljević, Branka and Šenerović, Lidija",
year = "2015",
abstract = "AimsThe aim of this study was to address the toxicity of recently described polyene macrolide 32, 33-didehydroroflamycoin (DDHR) on a wide range of fungal pathogens and its potential to control plant fungal diseases. Methods and ResultsThe antifungal activity of DDHR invitro was examined against common human and plant pathogenic fungi using a broth microdilution assay and a disk diffusion assay. Minimum inhibitory concentrations ranged from 125 to 35gml(-1). A radial growth inhibition assay showed that DDHR inhibited mycelia growth, inducing mycelial necrosis and affecting sporulation. During the invivo assay on apple fruits administration of DDHR 1h before fungal inoculation inhibited spreading of the infection. Importantly, DDHR exhibited no phytotoxic effects on the model plant, Capsicum annum, verified by the plant growth rate and chlorophyll content. ConclusionsDDHR inhibits growth of various plant pathogens invitro with the strongest activity against Alternaria alternata, Colletotrichum acutatum and Penicillium expansum, and protects apple fruits from decay. Significance and Impact of the StudyThis is the first report of the inhibitory effect of DDHR on important pathogenic fungal isolates. DDHR could be a good scaffold for developing new antifungal agents for fruit and vegetable protection.",
publisher = "Wiley, Hoboken",
journal = "Journal of Applied Microbiology",
title = "Control of human and plant fungal pathogens using pentaene macrolide 32, 33-didehydroroflamycoin",
pages = "1434-1426",
number = "6",
volume = "118",
doi = "10.1111/jam.12811"
}

Milisavljević, M., Zivković, S., Pekmezović, M., Stanković, N., Vojnović, S., Vasiljević, B.,& Šenerović, L.. (2015). Control of human and plant fungal pathogens using pentaene macrolide 32, 33-didehydroroflamycoin. in Journal of Applied Microbiology
Wiley, Hoboken., 118(6), 1426-1434.
https://doi.org/10.1111/jam.12811

Milisavljević M, Zivković S, Pekmezović M, Stanković N, Vojnović S, Vasiljević B, Šenerović L. Control of human and plant fungal pathogens using pentaene macrolide 32, 33-didehydroroflamycoin. in Journal of Applied Microbiology. 2015;118(6):1426-1434.
doi:10.1111/jam.12811 .

Milisavljević, Mira, Zivković, S., Pekmezović, M., Stanković, Nada, Vojnović, Sandra, Vasiljević, Branka, Šenerović, Lidija, "Control of human and plant fungal pathogens using pentaene macrolide 32, 33-didehydroroflamycoin" in Journal of Applied Microbiology, 118, no. 6 (2015):1426-1434,
https://doi.org/10.1111/jam.12811 . .