TY  - JOUR
AU  - Isaković, Anđelka M.
AU  - Petričević, Saša
AU  - Ristić, Slavica M.
AU  - Popadić, Dušan
AU  - Kravić-Stevović, Tamara
AU  - Zogović, Nevena
AU  - Poljarević, Jelena
AU  - Živanović-Radnić, Tatjana
AU  - Sabo, Tibor
AU  - Isaković, Aleksandra J.
AU  - Marković, Ivanka
AU  - Trajković, Vladimir S.
AU  - Misirlić-Denčić, Sonja
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2086
AB  - Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O, O-diethyl-(S, S)-ethylenediamineN, N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspasedependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
PB  - Lippincott Williams & Wilkins, Philadelphia
T2  - Melanoma Research
T1  - In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid
VL  - 28
IS  - 1
SP  - 8
EP  - 20
DO  - 10.1097/CMR.0000000000000409
ER  - 

@article{
author = "Isaković, Anđelka M. and Petričević, Saša and Ristić, Slavica M. and Popadić, Dušan and Kravić-Stevović, Tamara and Zogović, Nevena and Poljarević, Jelena and Živanović-Radnić, Tatjana and Sabo, Tibor and Isaković, Aleksandra J. and Marković, Ivanka and Trajković, Vladimir S. and Misirlić-Denčić, Sonja",
year = "2018",
abstract = "Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O, O-diethyl-(S, S)-ethylenediamineN, N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspasedependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.",
publisher = "Lippincott Williams & Wilkins, Philadelphia",
journal = "Melanoma Research",
title = "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid",
volume = "28",
number = "1",
pages = "8-20",
doi = "10.1097/CMR.0000000000000409"
}

Isaković, A. M., Petričević, S., Ristić, S. M., Popadić, D., Kravić-Stevović, T., Zogović, N., Poljarević, J., Živanović-Radnić, T., Sabo, T., Isaković, A. J., Marković, I., Trajković, V. S.,& Misirlić-Denčić, S.. (2018). In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid. in Melanoma Research
Lippincott Williams & Wilkins, Philadelphia., 28(1), 8-20.
https://doi.org/10.1097/CMR.0000000000000409

Isaković AM, Petričević S, Ristić SM, Popadić D, Kravić-Stevović T, Zogović N, Poljarević J, Živanović-Radnić T, Sabo T, Isaković AJ, Marković I, Trajković VS, Misirlić-Denčić S. In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid. in Melanoma Research. 2018;28(1):8-20.
doi:10.1097/CMR.0000000000000409 .

Isaković, Anđelka M., Petričević, Saša, Ristić, Slavica M., Popadić, Dušan, Kravić-Stevović, Tamara, Zogović, Nevena, Poljarević, Jelena, Živanović-Radnić, Tatjana, Sabo, Tibor, Isaković, Aleksandra J., Marković, Ivanka, Trajković, Vladimir S., Misirlić-Denčić, Sonja, "In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid" in Melanoma Research, 28, no. 1 (2018):8-20,
https://doi.org/10.1097/CMR.0000000000000409 . .

TY  - DATA
AU  - Dinić, Jelena
AU  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3616
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-biological Interactions
T1  - Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Vajs, V.; Tešević, V.; Isaković, A.; Pešić, M. Structural Differences in Diarylheptanoids Analogues from Alnus Viridis and Alnus Glutinosa Influence Their Activity and Selectivity towards Cancer Cells. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3616
ER  - 

@misc{
author = "Dinić, Jelena and Novaković, Miroslav M. and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra J. and Pešić, Milica",
year = "2016",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-biological Interactions",
title = "Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Vajs, V.; Tešević, V.; Isaković, A.; Pešić, M. Structural Differences in Diarylheptanoids Analogues from Alnus Viridis and Alnus Glutinosa Influence Their Activity and Selectivity towards Cancer Cells. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3616"
}

Dinić, J., Novaković, M. M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A. J.,& Pešić, M.. (2016). Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Vajs, V.; Tešević, V.; Isaković, A.; Pešić, M. Structural Differences in Diarylheptanoids Analogues from Alnus Viridis and Alnus Glutinosa Influence Their Activity and Selectivity towards Cancer Cells. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019. in Chemico-biological Interactions
Elsevier Ireland Ltd, Clare..
https://hdl.handle.net/21.15107/rcub_cherry_3616

Dinić J, Novaković MM, Podolski-Renić A, Vajs V, Tešević V, Isaković AJ, Pešić M. Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Vajs, V.; Tešević, V.; Isaković, A.; Pešić, M. Structural Differences in Diarylheptanoids Analogues from Alnus Viridis and Alnus Glutinosa Influence Their Activity and Selectivity towards Cancer Cells. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019. in Chemico-biological Interactions. 2016;.
https://hdl.handle.net/21.15107/rcub_cherry_3616 .

Dinić, Jelena, Novaković, Miroslav M., Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra J., Pešić, Milica, "Supplementary material for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Vajs, V.; Tešević, V.; Isaković, A.; Pešić, M. Structural Differences in Diarylheptanoids Analogues from Alnus Viridis and Alnus Glutinosa Influence Their Activity and Selectivity towards Cancer Cells. Chemico-Biological Interactions 2016, 249, 36–45. https://doi.org/10.1016/j.cbi.2016.02.019" in Chemico-biological Interactions (2016),
https://hdl.handle.net/21.15107/rcub_cherry_3616 .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Vajs, Vlatka
AU  - Tešević, Vele
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2066
AB  - Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-biological Interactions
T1  - Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells
VL  - 249
SP  - 36
EP  - 45
DO  - 10.1016/j.cbi.2016.02.019
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav M. and Podolski-Renić, Ana and Vajs, Vlatka and Tešević, Vele and Isaković, Aleksandra J. and Pešić, Milica",
year = "2016",
abstract = "Diarylheptanoids represent a group of plant secondary metabolites that possess multiple biological properties and are increasingly recognized for their therapeutic potential. A comparative study was performed on structurally analogous diarylheptanoids isolated from the bark of green (Alnus viridis) and black alder (Alnus glutinosa) to address their biological effects and determine structure-activity relationship. The structures and configurations of all compounds were elucidated by NMR, HR-ESI-MS, UV and IR. Diarylheptanoids actions were studied in human non-small cell lung carcinoma cells (NCI-H460) and normal keratinocytes (HaCaT). A. viridis compounds 3v, 5v, 8v and 9v that possess a carbonyl group at C-3 were considerably more potent than compounds without this group. A. viridis/A. glutinosa analogue pairs, 5v/5g and 9v/9g, which differ in the presence of 30 and 300-OH groups, were evaluated for anticancer activity and selectivity. 5v and 9v that do not possess 30 and 300-OH groups showed significantly higher cytotoxicity compared to analogues 5g and 9g. In addition, these two A. viridis compounds induced a more prominent apoptosis in both cell lines and an increase in subG0 cell cycle phase, compared to their A. glutinosa analogues. 5v and 9v treatment triggered intracellular superoxide anion accumulation and notably decreased mitochondrial transmembrane potential. In HaCaT cells, 9v and 9g with a 4,5 double bond caused a more prominent loss of mitochondrial transmembrane potential compared to 5v and 5g which possess a 5-methoxy group instead. Although green alder diarylheptanoids 5v and 9v displayed higher cytotoxicity, their analogues from black alder 5g and 9g could be more favorable for therapeutic use since they were more active in cancer cells than in normal keratinocytes. These results indicate that minor differences in the chemical structure can greatly influence the effect of diarylheptanoids on apoptosis and redox status and determine their selectivity towards cancer cells. (C) 2016 Elsevier Ireland Ltd. All rights reserved.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-biological Interactions",
title = "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells",
volume = "249",
pages = "36-45",
doi = "10.1016/j.cbi.2016.02.019"
}

Dinić, J., Novaković, M. M., Podolski-Renić, A., Vajs, V., Tešević, V., Isaković, A. J.,& Pešić, M.. (2016). Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-biological Interactions
Elsevier Ireland Ltd, Clare., 249, 36-45.
https://doi.org/10.1016/j.cbi.2016.02.019

Dinić J, Novaković MM, Podolski-Renić A, Vajs V, Tešević V, Isaković AJ, Pešić M. Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells. in Chemico-biological Interactions. 2016;249:36-45.
doi:10.1016/j.cbi.2016.02.019 .

Dinić, Jelena, Novaković, Miroslav M., Podolski-Renić, Ana, Vajs, Vlatka, Tešević, Vele, Isaković, Aleksandra J., Pešić, Milica, "Structural differences in diarylheptanoids analogues from Alnus viridis and Alnus glutinosa influence their activity and selectivity towards cancer cells" in Chemico-biological Interactions, 249 (2016):36-45,
https://doi.org/10.1016/j.cbi.2016.02.019 . .

TY  - JOUR
AU  - Trifunović, Snežana S.
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra J.
AU  - Vučković, Ivan M.
AU  - Mandić, Boris
AU  - Novaković, Miroslav M.
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
AU  - Trajković, Vladimir S.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1511
AB  - Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 297
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana S. and Isaković, Anđelka M. and Isaković, Aleksandra J. and Vučković, Ivan M. and Mandić, Boris and Novaković, Miroslav M. and Vajs, Vlatka and Milosavljević, Slobodan M. and Trajković, Vladimir S.",
year = "2014",
abstract = "Further phytochemical investigation of the aerial parts of Achillea clavennae has resulted in the isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and the iso-seco-guaianolide 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known compounds were also found, of which 9-acetoxycanin (5), sintenin (6), and oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were elucidated by combined spectroscopic methods (1D and 2DNMR, HRESIMS, CIMS, and FTIR). While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "297-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S. S., Isaković, A. M., Isaković, A. J., Vučković, I. M., Mandić, B., Novaković, M. M., Vajs, V., Milosavljević, S. M.,& Trajković, V. S.. (2014). Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart., 80(4), 297-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović SS, Isaković AM, Isaković AJ, Vučković IM, Mandić B, Novaković MM, Vajs V, Milosavljević SM, Trajković VS. Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae. in Planta Medica. 2014;80(4):297-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana S., Isaković, Anđelka M., Isaković, Aleksandra J., Vučković, Ivan M., Mandić, Boris, Novaković, Miroslav M., Vajs, Vlatka, Milosavljević, Slobodan M., Trajković, Vladimir S., "Isolation, Characterization, and In Vitro Cytotoxicity of New Sesquiterpenoids from Achillea clavennae" in Planta Medica, 80, no. 4 (2014):297-305,
https://doi.org/10.1055/s-0033-1360312 . .

TY  - JOUR
AU  - Trifunović, Snežana S.
AU  - Isaković, Anđelka M.
AU  - Isaković, Aleksandra J.
AU  - Vučković, Ivan M.
AU  - Mandić, Boris
AU  - Novaković, Miroslav M.
AU  - Vajs, Vlatka
AU  - Milosavljević, Slobodan M.
AU  - Trajković, Vladimir S.
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2816
AB  - Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 
isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 
the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 
compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 
oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 
elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 
While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 
seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 
apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.
PB  - Georg Thieme Verlag
T2  - Planta medica
T1  - Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae
VL  - 80
IS  - 4
SP  - 275
EP  - 305
DO  - 10.1055/s-0033-1360312
ER  - 

@article{
author = "Trifunović, Snežana S. and Isaković, Anđelka M. and Isaković, Aleksandra J. and Vučković, Ivan M. and Mandić, Boris and Novaković, Miroslav M. and Vajs, Vlatka and Milosavljević, Slobodan M. and Trajković, Vladimir S.",
year = "2014",
abstract = "Further phytochemical investigation into the aerial parts of Achillea clavennae has resulted in the 3 
isolation of three new sesquiterpene lactones: two highly oxygenated germacranolides (1, 2) and 4 
the iso-seco-guaianolide, 9(R)-acetoxy-3-O-methyl-iso-seco-tanapartholide (3). Eight known 5 
compounds were also found in this plant species, of which 9 α -acetoxycanin (5), sintenin (6) and 6 
oleanolic acid (7) were detected for the first time. The structures of the isolated compounds were 7 
elucidated by combined spectroscopic methods (1D and 2D NMR, HRESIMS, CIMS, FTIR). 8 
While the predominant metabolite germacranolide sintenin (6) was not cytotoxic, the new iso-9 
seco-guaianolide (3) displayed cytotoxicity comparable to that of cisplatin and the lactone 10 
apressin (4), inducing partly apoptotic death in human U251 and rat C6 glioma cell lines.",
publisher = "Georg Thieme Verlag",
journal = "Planta medica",
title = "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae",
volume = "80",
number = "4",
pages = "275-305",
doi = "10.1055/s-0033-1360312"
}

Trifunović, S. S., Isaković, A. M., Isaković, A. J., Vučković, I. M., Mandić, B., Novaković, M. M., Vajs, V., Milosavljević, S. M.,& Trajković, V. S.. (2014). Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica
Georg Thieme Verlag., 80(4), 275-305.
https://doi.org/10.1055/s-0033-1360312

Trifunović SS, Isaković AM, Isaković AJ, Vučković IM, Mandić B, Novaković MM, Vajs V, Milosavljević SM, Trajković VS. Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae. in Planta medica. 2014;80(4):275-305.
doi:10.1055/s-0033-1360312 .

Trifunović, Snežana S., Isaković, Anđelka M., Isaković, Aleksandra J., Vučković, Ivan M., Mandić, Boris, Novaković, Miroslav M., Vajs, Vlatka, Milosavljević, Slobodan M., Trajković, Vladimir S., "Isolation, characterization and in vitro cytotoxicity of new sesquiterpenoids from Achillea clavennae" in Planta medica, 80, no. 4 (2014):275-305,
https://doi.org/10.1055/s-0033-1360312 . .

TY  - DATA
AU  - Dinić, Jelena
AU  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Stojković, Sonja
AU  - Mandić, Boris
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3677
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, S.; Mandić, B.; Tešević, V.; Vajs, V.; Isaković, A.; Pešić, M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus Glutinosa) and Their Interaction with Anticancer Drugs. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3677
ER  - 

@misc{
author = "Dinić, Jelena and Novaković, Miroslav M. and Podolski-Renić, Ana and Stojković, Sonja and Mandić, Boris and Tešević, Vele and Vajs, Vlatka and Isaković, Aleksandra J. and Pešić, Milica",
year = "2014",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, S.; Mandić, B.; Tešević, V.; Vajs, V.; Isaković, A.; Pešić, M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus Glutinosa) and Their Interaction with Anticancer Drugs. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3677"
}

Dinić, J., Novaković, M. M., Podolski-Renić, A., Stojković, S., Mandić, B., Tešević, V., Vajs, V., Isaković, A. J.,& Pešić, M.. (2014). Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, S.; Mandić, B.; Tešević, V.; Vajs, V.; Isaković, A.; Pešić, M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus Glutinosa) and Their Interaction with Anticancer Drugs. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart..
https://hdl.handle.net/21.15107/rcub_cherry_3677

Dinić J, Novaković MM, Podolski-Renić A, Stojković S, Mandić B, Tešević V, Vajs V, Isaković AJ, Pešić M. Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, S.; Mandić, B.; Tešević, V.; Vajs, V.; Isaković, A.; Pešić, M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus Glutinosa) and Their Interaction with Anticancer Drugs. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993. in Planta Medica. 2014;.
https://hdl.handle.net/21.15107/rcub_cherry_3677 .

Dinić, Jelena, Novaković, Miroslav M., Podolski-Renić, Ana, Stojković, Sonja, Mandić, Boris, Tešević, Vele, Vajs, Vlatka, Isaković, Aleksandra J., Pešić, Milica, "Supplementary data for the article: Dinić, J.; Novaković, M.; Podolski-Renić, A.; Stojković, S.; Mandić, B.; Tešević, V.; Vajs, V.; Isaković, A.; Pešić, M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus Glutinosa) and Their Interaction with Anticancer Drugs. Planta Medica 2014, 80 (13), 1088–1096. https://doi.org/10.1055/s-0034-1382993" in Planta Medica (2014),
https://hdl.handle.net/21.15107/rcub_cherry_3677 .

TY  - JOUR
AU  - Dinić, Jelena
AU  - Novaković, Miroslav M.
AU  - Podolski-Renić, Ana
AU  - Stojković, Sonja
AU  - Mandić, Boris
AU  - Tešević, Vele
AU  - Vajs, Vlatka
AU  - Isaković, Aleksandra J.
AU  - Pešić, Milica
PY  - 2014
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1845
AB  - Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI-H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1 alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1 alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.
PB  - Georg Thieme Verlag Kg, Stuttgart
T2  - Planta Medica
T1  - Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs
VL  - 80
IS  - 13
SP  - 1088
EP  - 1096
DO  - 10.1055/s-0034-1382993
ER  - 

@article{
author = "Dinić, Jelena and Novaković, Miroslav M. and Podolski-Renić, Ana and Stojković, Sonja and Mandić, Boris and Tešević, Vele and Vajs, Vlatka and Isaković, Aleksandra J. and Pešić, Milica",
year = "2014",
abstract = "Diarylheptanoids belong to polyphenols, a group of plant secondary metabolites with multiple biological properties. Many of them display antioxidative, cytotoxic, or anticancer actions and are increasingly recognized as potential therapeutic agents. The aim of this study was to evaluate antioxidant and cytoprotective activity of two diarylheptanoids: platyphylloside 5(S)-1,7-di(4-hydroxyphenyl)-3-heptanone-5-O-beta-D-glucopyranoside (1) and its newly discovered analog 5(S)-1,7-di(4-hydroxyphenyl)-5-O-beta-D-[6-(E-p-coumaroylglucopyranosyl)]heptane-3-one (2), both isolated from the bark of black alder (Alnus glutinosa). To that end, we have employed a cancer cell line (NCI-H460), normal human keratinocytes (HaCaT), and peripheral blood mononuclear cells. The effects on cell growth were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Cell death was examined by annexin V/propidium iodide staining on a flow cytometer. Reactive oxygen species production was examined by dihydroethidium staining. Mitochondrial structure and doxorubicin localization were visualized by fluorescent microscopy. Gene expression of manganese superoxide dismutase and hypoxia-inducible factor-1 alpha was determined by reverse transcription polymerase chain reaction. Diarylheptanoids antagonized the effects of either doxorubicin or cisplatin, significantly increasing their IC50 values in normal cells. Diarylheptanoid 1 induced the retention of doxorubicin in cytoplasm and reduced mitochondrial fragmentation associated with doxorubicin application. Diarylheptanoid 2 reduced the reactive oxygen species production induced by cisplatin. Both compounds increased the messenger ribonucleic acid expression of enzymes involved in reactive oxygen species elimination (manganese superoxide dismutase and hypoxia-inducible factor-1 alpha). These results indicate that neutralization of reactive oxygen species is an important mechanism of diarylheptanoid action, although these compounds exert a considerable anticancer effect. Therefore, these compounds may serve as protectors of normal cells during chemotherapy without significantly diminishing the effect of the applied chemotherapeutic.",
publisher = "Georg Thieme Verlag Kg, Stuttgart",
journal = "Planta Medica",
title = "Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs",
volume = "80",
number = "13",
pages = "1088-1096",
doi = "10.1055/s-0034-1382993"
}

Dinić, J., Novaković, M. M., Podolski-Renić, A., Stojković, S., Mandić, B., Tešević, V., Vajs, V., Isaković, A. J.,& Pešić, M.. (2014). Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs. in Planta Medica
Georg Thieme Verlag Kg, Stuttgart., 80(13), 1088-1096.
https://doi.org/10.1055/s-0034-1382993

Dinić J, Novaković MM, Podolski-Renić A, Stojković S, Mandić B, Tešević V, Vajs V, Isaković AJ, Pešić M. Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs. in Planta Medica. 2014;80(13):1088-1096.
doi:10.1055/s-0034-1382993 .

Dinić, Jelena, Novaković, Miroslav M., Podolski-Renić, Ana, Stojković, Sonja, Mandić, Boris, Tešević, Vele, Vajs, Vlatka, Isaković, Aleksandra J., Pešić, Milica, "Antioxidative Activity of Diarylheptanoids from the Bark of Black Alder (Alnus glutinosa) and Their Interaction with Anticancer Drugs" in Planta Medica, 80, no. 13 (2014):1088-1096,
https://doi.org/10.1055/s-0034-1382993 . .

TY  - JOUR
AU  - Misirlić-Denčić, Sonja
AU  - Poljarević, Jelena
AU  - Vilimanovich, Urosh
AU  - Bogdanović, Andrija
AU  - Isaković, Aleksandra J.
AU  - Kravić-Stevović, Tamara
AU  - Dulović, Marija
AU  - Zogović, Nevena
AU  - Isaković, Anđelka M.
AU  - Grgurić-Šipka, Sanja
AU  - Bumbasirevic, Vladimir
AU  - Sabo, Tibor
AU  - Trajković, Vladimir S.
AU  - Marković, Ivanka
PY  - 2012
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/1279
AB  - We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.
PB  - Amer Chemical Soc, Washington
T2  - Chemical Research in Toxicology
T1  - Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells
VL  - 25
IS  - 4
SP  - 931
EP  - 939
DO  - 10.1021/tx3000329
ER  - 

@article{
author = "Misirlić-Denčić, Sonja and Poljarević, Jelena and Vilimanovich, Urosh and Bogdanović, Andrija and Isaković, Aleksandra J. and Kravić-Stevović, Tamara and Dulović, Marija and Zogović, Nevena and Isaković, Anđelka M. and Grgurić-Šipka, Sanja and Bumbasirevic, Vladimir and Sabo, Tibor and Trajković, Vladimir S. and Marković, Ivanka",
year = "2012",
abstract = "We investigated the cytotoxicity of recently synthesized (S,S)-ethyleridiamine-N,N'-di-2-(3-cyclohexyl)propanoic acid esters toward human leukemic cell lines and healthy blood mononuclear cells. Cell viability was assessed by acid phosphatase assay, apoptosis, and differentiation were analyzed by flow cytometry and electron microscopy, while intracellular localization of apoptosis-inducing factor (AIF) was determined by immunoblotting. It was demonstrated that methyl, ethyl, and n-propyl esters were toxic to HL-60, REH, MOLT-4, KG-1, JVM-2, and K-562 leukemic cell lines, while the nonesterified parental compound and n-butyl ester were devoid of cytotoxic action. The ethyl ester exhibited the highest cytotoxic activity (IC50 10.7 mu M-45.4 mu M), which was comparable to that of the prototypical anticancer drug cisplatin. The observed cytotoxic effect in HL-60 cells was associated with an increase in superoxide production and mitochondrial membrane depolarization, leading to apoptotic cell death characterized by phosphatidylserine externalization and DNA fragmentation in the absence of autophagic response. DNA fragmentation preceded caspase activation and followed AIF translocation from mitochondria to nucleus, which was indicative of caspase-independent apoptotic cell death. HL-60 cells treated with subtoxic concentration of the compound displayed morphological signs of granulocytic differentiation (nuclear indentations and presence of cytoplasmic primary granules), as well as an increased expression of differentiation markers CD11b and CD15. The cyclohexyl analogues of ethylenediamine dipropanoic acid were also toxic to peripheral blood mononuclear cells of both healthy controls and leukemic patients, the latter being more sensitive. Our data demonstrate that the toxicity of the investigated cyclohexyl compounds against leukemic cell lines is mediated by caspase-independent apoptosis associated with oxidative stress, mitochondrial dysfunction, and AIF translocation.",
publisher = "Amer Chemical Soc, Washington",
journal = "Chemical Research in Toxicology",
title = "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells",
volume = "25",
number = "4",
pages = "931-939",
doi = "10.1021/tx3000329"
}

Misirlić-Denčić, S., Poljarević, J., Vilimanovich, U., Bogdanović, A., Isaković, A. J., Kravić-Stevović, T., Dulović, M., Zogović, N., Isaković, A. M., Grgurić-Šipka, S., Bumbasirevic, V., Sabo, T., Trajković, V. S.,& Marković, I.. (2012). Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology
Amer Chemical Soc, Washington., 25(4), 931-939.
https://doi.org/10.1021/tx3000329

Misirlić-Denčić S, Poljarević J, Vilimanovich U, Bogdanović A, Isaković AJ, Kravić-Stevović T, Dulović M, Zogović N, Isaković AM, Grgurić-Šipka S, Bumbasirevic V, Sabo T, Trajković VS, Marković I. Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells. in Chemical Research in Toxicology. 2012;25(4):931-939.
doi:10.1021/tx3000329 .

Misirlić-Denčić, Sonja, Poljarević, Jelena, Vilimanovich, Urosh, Bogdanović, Andrija, Isaković, Aleksandra J., Kravić-Stevović, Tamara, Dulović, Marija, Zogović, Nevena, Isaković, Anđelka M., Grgurić-Šipka, Sanja, Bumbasirevic, Vladimir, Sabo, Tibor, Trajković, Vladimir S., Marković, Ivanka, "Cyclohexyl Analogues of Ethylenediamine Dipropanoic Acid Induce Caspase-Independent Mitochondrial Apoptosis in Human Leukemic Cells" in Chemical Research in Toxicology, 25, no. 4 (2012):931-939,
https://doi.org/10.1021/tx3000329 . .