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 . .