TY  - CONF
AU  - Ružić, Dušan
AU  - Petković, Miloš
AU  - Đoković, Nemanja
AU  - Santibanez, Juan
AU  - Pavić, Aleksandar
AU  - Ganesan, A.
AU  - Srdić Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5074
AB  - Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that has poor survival rates due to the absence of specific molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In the era of precision oncology, it is recognized that an imbalance in post-translational modifications of histones, such as histone lysine acetylation and deacetylation, is closely linked to tumor initiation and progression. Two groups of enzymes control the reversible nature of histone post-translational acetylation: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Isoform-specific targeting of HDACs is considered a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, non-selective HDAC inhibitors have been more extensively studied in clinical trials. This work presents the design and discovery of potent HDAC inhibitors that selectively target HDAC6 isozyme, using 1-benzhydryl piperazine as a surface recognition group with different hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with nanomolar IC50 values and two non-selective HDAC inhibitors were identified. Structure-based molecular modelling was utilized to investigate the impact of linker chemistry on the potency of synthesized inhibitors against HDAC6. The anti-cancer, anti-migratory, and anti-invasive activities of these compounds were evaluated using breast cancer cell lines (MDA-MB-231 and MCF-7). Experiments on a zebrafish MDA-MB-231 xenograft model demonstrated that a novel non-selective HDAC inhibitor (8b) with a seven-carbon-atom linker exhibited potent effects against tumor growth, metastasis, and angiogenesis at low micromolar concentrations.
PB  - Serbian Association on for Cancer Research Belgrade, Serbia
C3  - Oncology
Insights
T1  - Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study
VL  - 1
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5074
ER  - 

@conference{
author = "Ružić, Dušan and Petković, Miloš and Đoković, Nemanja and Santibanez, Juan and Pavić, Aleksandar and Ganesan, A. and Srdić Rajić, Tatjana and Nikolić, Katarina",
year = "2023",
abstract = "Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that has poor survival rates due to the absence of specific molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In the era of precision oncology, it is recognized that an imbalance in post-translational modifications of histones, such as histone lysine acetylation and deacetylation, is closely linked to tumor initiation and progression. Two groups of enzymes control the reversible nature of histone post-translational acetylation: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Isoform-specific targeting of HDACs is considered a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, non-selective HDAC inhibitors have been more extensively studied in clinical trials. This work presents the design and discovery of potent HDAC inhibitors that selectively target HDAC6 isozyme, using 1-benzhydryl piperazine as a surface recognition group with different hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with nanomolar IC50 values and two non-selective HDAC inhibitors were identified. Structure-based molecular modelling was utilized to investigate the impact of linker chemistry on the potency of synthesized inhibitors against HDAC6. The anti-cancer, anti-migratory, and anti-invasive activities of these compounds were evaluated using breast cancer cell lines (MDA-MB-231 and MCF-7). Experiments on a zebrafish MDA-MB-231 xenograft model demonstrated that a novel non-selective HDAC inhibitor (8b) with a seven-carbon-atom linker exhibited potent effects against tumor growth, metastasis, and angiogenesis at low micromolar concentrations.",
publisher = "Serbian Association on for Cancer Research Belgrade, Serbia",
journal = "Oncology
Insights",
title = "Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study",
volume = "1",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5074"
}

Ružić, D., Petković, M., Đoković, N., Santibanez, J., Pavić, A., Ganesan, A., Srdić Rajić, T.,& Nikolić, K.. (2023). Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study. in Oncology
Insights
Serbian Association on for Cancer Research Belgrade, Serbia., 1.
https://hdl.handle.net/21.15107/rcub_farfar_5074

Ružić D, Petković M, Đoković N, Santibanez J, Pavić A, Ganesan A, Srdić Rajić T, Nikolić K. Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study. in Oncology
Insights. 2023;1.
https://hdl.handle.net/21.15107/rcub_farfar_5074 .

Ružić, Dušan, Petković, Miloš, Đoković, Nemanja, Santibanez, Juan, Pavić, Aleksandar, Ganesan, A., Srdić Rajić, Tatjana, Nikolić, Katarina, "Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study" in Oncology
Insights, 1 (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5074 .

TY  - GEN
AU  - Ružić, Dušan
AU  - Ellinger, Bernhard
AU  - Đoković, Nemanja
AU  - Santibanez, Juan
AU  - Ganesan, A.
AU  - Pavić, Aleksandar
AU  - Srdić Rajić, Tatjana
AU  - Petković, Miloš
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4951
PB  - Institute Pasteur, France
T2  - Journal Club on Drug Design, Institute Pasteur, Paris, France November 25 2022
T1  - Identification of novel 1-benzhydryl-piperazine derivatives as Histone Deacetylase inhibitors using Fragment-based drug design strategy
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4951
ER  - 

@misc{
author = "Ružić, Dušan and Ellinger, Bernhard and Đoković, Nemanja and Santibanez, Juan and Ganesan, A. and Pavić, Aleksandar and Srdić Rajić, Tatjana and Petković, Miloš and Nikolić, Katarina",
year = "2022",
publisher = "Institute Pasteur, France",
journal = "Journal Club on Drug Design, Institute Pasteur, Paris, France November 25 2022",
title = "Identification of novel 1-benzhydryl-piperazine derivatives as Histone Deacetylase inhibitors using Fragment-based drug design strategy",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4951"
}

Ružić, D., Ellinger, B., Đoković, N., Santibanez, J., Ganesan, A., Pavić, A., Srdić Rajić, T., Petković, M.,& Nikolić, K.. (2022). Identification of novel 1-benzhydryl-piperazine derivatives as Histone Deacetylase inhibitors using Fragment-based drug design strategy. in Journal Club on Drug Design, Institute Pasteur, Paris, France November 25 2022
Institute Pasteur, France..
https://hdl.handle.net/21.15107/rcub_farfar_4951

Ružić D, Ellinger B, Đoković N, Santibanez J, Ganesan A, Pavić A, Srdić Rajić T, Petković M, Nikolić K. Identification of novel 1-benzhydryl-piperazine derivatives as Histone Deacetylase inhibitors using Fragment-based drug design strategy. in Journal Club on Drug Design, Institute Pasteur, Paris, France November 25 2022. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4951 .

Ružić, Dušan, Ellinger, Bernhard, Đoković, Nemanja, Santibanez, Juan, Ganesan, A., Pavić, Aleksandar, Srdić Rajić, Tatjana, Petković, Miloš, Nikolić, Katarina, "Identification of novel 1-benzhydryl-piperazine derivatives as Histone Deacetylase inhibitors using Fragment-based drug design strategy" in Journal Club on Drug Design, Institute Pasteur, Paris, France November 25 2022 (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4951 .

TY  - CONF
AU  - Ružić, Dušan
AU  - Đoković, Nemanja
AU  - Corentin, Bon
AU  - Petković, Miloš
AU  - Ellinger, Bertrand
AU  - Gul, Sheraz
AU  - Santibanez, Juan
AU  - Lahtela-Kakkonen, Maija
AU  - Halby, Ludovic
AU  - Ganesan, A.
AU  - Srdić Rajić, Tatjana
AU  - Arimondo, Paola
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4938
C3  - e-EuCo-CTC 2021, Online conference, EuChemS Division of Computational and Theoretical Chemistry, November 18-19 2021
T1  - Epigenetic drug discovery: Successful examples of Computer-Aided Drug Designing of Histone Deacetylase (HDAC6 and SIRT2) and Histone Methyltransferase (DOT1L) inhibitors
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4938
ER  - 

@conference{
author = "Ružić, Dušan and Đoković, Nemanja and Corentin, Bon and Petković, Miloš and Ellinger, Bertrand and Gul, Sheraz and Santibanez, Juan and Lahtela-Kakkonen, Maija and Halby, Ludovic and Ganesan, A. and Srdić Rajić, Tatjana and Arimondo, Paola and Nikolić, Katarina",
year = "2021",
journal = "e-EuCo-CTC 2021, Online conference, EuChemS Division of Computational and Theoretical Chemistry, November 18-19 2021",
title = "Epigenetic drug discovery: Successful examples of Computer-Aided Drug Designing of Histone Deacetylase (HDAC6 and SIRT2) and Histone Methyltransferase (DOT1L) inhibitors",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4938"
}

Ružić, D., Đoković, N., Corentin, B., Petković, M., Ellinger, B., Gul, S., Santibanez, J., Lahtela-Kakkonen, M., Halby, L., Ganesan, A., Srdić Rajić, T., Arimondo, P.,& Nikolić, K.. (2021). Epigenetic drug discovery: Successful examples of Computer-Aided Drug Designing of Histone Deacetylase (HDAC6 and SIRT2) and Histone Methyltransferase (DOT1L) inhibitors. in e-EuCo-CTC 2021, Online conference, EuChemS Division of Computational and Theoretical Chemistry, November 18-19 2021.
https://hdl.handle.net/21.15107/rcub_farfar_4938

Ružić D, Đoković N, Corentin B, Petković M, Ellinger B, Gul S, Santibanez J, Lahtela-Kakkonen M, Halby L, Ganesan A, Srdić Rajić T, Arimondo P, Nikolić K. Epigenetic drug discovery: Successful examples of Computer-Aided Drug Designing of Histone Deacetylase (HDAC6 and SIRT2) and Histone Methyltransferase (DOT1L) inhibitors. in e-EuCo-CTC 2021, Online conference, EuChemS Division of Computational and Theoretical Chemistry, November 18-19 2021. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_4938 .

Ružić, Dušan, Đoković, Nemanja, Corentin, Bon, Petković, Miloš, Ellinger, Bertrand, Gul, Sheraz, Santibanez, Juan, Lahtela-Kakkonen, Maija, Halby, Ludovic, Ganesan, A., Srdić Rajić, Tatjana, Arimondo, Paola, Nikolić, Katarina, "Epigenetic drug discovery: Successful examples of Computer-Aided Drug Designing of Histone Deacetylase (HDAC6 and SIRT2) and Histone Methyltransferase (DOT1L) inhibitors" in e-EuCo-CTC 2021, Online conference, EuChemS Division of Computational and Theoretical Chemistry, November 18-19 2021 (2021),
https://hdl.handle.net/21.15107/rcub_farfar_4938 .

TY  - CONF
AU  - Ružić, Dušan
AU  - Petković, Miloš
AU  - Gul, Sheraz
AU  - Santibanez, Juan
AU  - Srdić-Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4942
PB  - European Association for Cancer Research
C3  - EACR 2021 Congress, Innovative Cancer Science: Better Outcomes Through Research, Virtual Congress, 9 – 12 June, 2021.
T1  - Novel 1-benzhydryl piperazine derivative inhibits the migration and invasiveness of breast cancer cells: Synthesis, molecular modelling and biological characterization
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4942
ER  - 

@conference{
author = "Ružić, Dušan and Petković, Miloš and Gul, Sheraz and Santibanez, Juan and Srdić-Rajić, Tatjana and Nikolić, Katarina",
year = "2021",
publisher = "European Association for Cancer Research",
journal = "EACR 2021 Congress, Innovative Cancer Science: Better Outcomes Through Research, Virtual Congress, 9 – 12 June, 2021.",
title = "Novel 1-benzhydryl piperazine derivative inhibits the migration and invasiveness of breast cancer cells: Synthesis, molecular modelling and biological characterization",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4942"
}

Ružić, D., Petković, M., Gul, S., Santibanez, J., Srdić-Rajić, T.,& Nikolić, K.. (2021). Novel 1-benzhydryl piperazine derivative inhibits the migration and invasiveness of breast cancer cells: Synthesis, molecular modelling and biological characterization. in EACR 2021 Congress, Innovative Cancer Science: Better Outcomes Through Research, Virtual Congress, 9 – 12 June, 2021.
European Association for Cancer Research..
https://hdl.handle.net/21.15107/rcub_farfar_4942

Ružić D, Petković M, Gul S, Santibanez J, Srdić-Rajić T, Nikolić K. Novel 1-benzhydryl piperazine derivative inhibits the migration and invasiveness of breast cancer cells: Synthesis, molecular modelling and biological characterization. in EACR 2021 Congress, Innovative Cancer Science: Better Outcomes Through Research, Virtual Congress, 9 – 12 June, 2021.. 2021;.
https://hdl.handle.net/21.15107/rcub_farfar_4942 .

Ružić, Dušan, Petković, Miloš, Gul, Sheraz, Santibanez, Juan, Srdić-Rajić, Tatjana, Nikolić, Katarina, "Novel 1-benzhydryl piperazine derivative inhibits the migration and invasiveness of breast cancer cells: Synthesis, molecular modelling and biological characterization" in EACR 2021 Congress, Innovative Cancer Science: Better Outcomes Through Research, Virtual Congress, 9 – 12 June, 2021. (2021),
https://hdl.handle.net/21.15107/rcub_farfar_4942 .

TY  - CONF
AU  - Ružić, Dušan
AU  - Petković, Miloš
AU  - Ellinger, Bernhard
AU  - Gul, Sheraz
AU  - Santibanez, Juan
AU  - Srdić-Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4890
AB  - Human epigenetic metalloenzymes that modulate the acetylation status of histones, alter cancer cell morphology
and cell survival are histone deacetylases (HDACs). Of particular importance, histone deacetylase 6 is studied as
a cytoplasmic isoform implicated in the microtubule dynamics in cancer 1. Still, more efforts need to be
undertaken to make these inhibitors reach to global oncology market 2. In this study, we probed the 1-benzhydryl
piperazine as the capping (CAP) group to selectively target the HDAC6 isoform and alter the migration and
invasiveness of the breast cancer cell lines. Nine different 1-benzhydryl piperazine derivatives were synthesized
and the structure-activity relationship study was postulated with combined ligand-based (3D-QSAR) and
structure-based (molecular docking) in silico approaches 3,4. We performed wound healing, matrigel invasion
and transwell migration assays to search for the inhibitor that shows antimigratory and antiinvasive properties of
the breast cancer cell lines (MDA-MB-231 and MCF-7). Most of the synthesized compounds induce apoptosis in
excellent non-cytotoxic, antimigratory and antiinvasive profile in breast cancer cell lines, which is in agreement
with the proposed cellular roles of HDAC6 in cancer. The work presented in this study integrates in silico modelling, synthesis and in vitro biological profiling to
discover selective HDAC6 inhibitor. Identification of potent HDAC6 inhibitor that alters migration and
invasiveness of breast cancer cell lines opens up new horizons to treat metastatic diseases.
PB  - EFMC-ISMC
C3  - EFMC-ISMC, XXVI EFMC International Symposium on Medicinal Chemistry, Book of Abstracts
T1  - Synthesis, molecular modelling and biological characterization of novel antimigratory and antiinvasive 1-benzhydryl piperazine derivatives
SP  - 372
EP  - 372
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4890
ER  - 

@conference{
author = "Ružić, Dušan and Petković, Miloš and Ellinger, Bernhard and Gul, Sheraz and Santibanez, Juan and Srdić-Rajić, Tatjana and Nikolić, Katarina",
year = "2021",
abstract = "Human epigenetic metalloenzymes that modulate the acetylation status of histones, alter cancer cell morphology
and cell survival are histone deacetylases (HDACs). Of particular importance, histone deacetylase 6 is studied as
a cytoplasmic isoform implicated in the microtubule dynamics in cancer 1. Still, more efforts need to be
undertaken to make these inhibitors reach to global oncology market 2. In this study, we probed the 1-benzhydryl
piperazine as the capping (CAP) group to selectively target the HDAC6 isoform and alter the migration and
invasiveness of the breast cancer cell lines. Nine different 1-benzhydryl piperazine derivatives were synthesized
and the structure-activity relationship study was postulated with combined ligand-based (3D-QSAR) and
structure-based (molecular docking) in silico approaches 3,4. We performed wound healing, matrigel invasion
and transwell migration assays to search for the inhibitor that shows antimigratory and antiinvasive properties of
the breast cancer cell lines (MDA-MB-231 and MCF-7). Most of the synthesized compounds induce apoptosis in
excellent non-cytotoxic, antimigratory and antiinvasive profile in breast cancer cell lines, which is in agreement
with the proposed cellular roles of HDAC6 in cancer. The work presented in this study integrates in silico modelling, synthesis and in vitro biological profiling to
discover selective HDAC6 inhibitor. Identification of potent HDAC6 inhibitor that alters migration and
invasiveness of breast cancer cell lines opens up new horizons to treat metastatic diseases.",
publisher = "EFMC-ISMC",
journal = "EFMC-ISMC, XXVI EFMC International Symposium on Medicinal Chemistry, Book of Abstracts",
title = "Synthesis, molecular modelling and biological characterization of novel antimigratory and antiinvasive 1-benzhydryl piperazine derivatives",
pages = "372-372",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4890"
}

Ružić, D., Petković, M., Ellinger, B., Gul, S., Santibanez, J., Srdić-Rajić, T.,& Nikolić, K.. (2021). Synthesis, molecular modelling and biological characterization of novel antimigratory and antiinvasive 1-benzhydryl piperazine derivatives. in EFMC-ISMC, XXVI EFMC International Symposium on Medicinal Chemistry, Book of Abstracts
EFMC-ISMC., 372-372.
https://hdl.handle.net/21.15107/rcub_farfar_4890

Ružić D, Petković M, Ellinger B, Gul S, Santibanez J, Srdić-Rajić T, Nikolić K. Synthesis, molecular modelling and biological characterization of novel antimigratory and antiinvasive 1-benzhydryl piperazine derivatives. in EFMC-ISMC, XXVI EFMC International Symposium on Medicinal Chemistry, Book of Abstracts. 2021;:372-372.
https://hdl.handle.net/21.15107/rcub_farfar_4890 .

Ružić, Dušan, Petković, Miloš, Ellinger, Bernhard, Gul, Sheraz, Santibanez, Juan, Srdić-Rajić, Tatjana, Nikolić, Katarina, "Synthesis, molecular modelling and biological characterization of novel antimigratory and antiinvasive 1-benzhydryl piperazine derivatives" in EFMC-ISMC, XXVI EFMC International Symposium on Medicinal Chemistry, Book of Abstracts (2021):372-372,
https://hdl.handle.net/21.15107/rcub_farfar_4890 .

TY  - CONF
AU  - Nikolić, Katarina
AU  - Ružić, Dušan
AU  - Beljkaš, Milan
AU  - Petković, Miloš
AU  - Gul, Sheraz
AU  - Santibanez, Juan
AU  - Srdić Rajić, Tatjana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4928
AB  - Academia and industry make an extensive effort to discover selective histone deacetylase 6 inhibitors (HDAC6i) which could be delivered to the patients. These attempts are partially obscured by inconsistency in preclinical data regarding the cellular and biochemical changes upon treatment of solid tumours with HDAC6i. In this study, we present computational design, synthesis of three novel HDAC6 inhibitors along with their in vitro pharmacological profile against zinc-dependent HDACs. The in vitro anticancer effects of the synthesized compounds were examined on four types of cancer cell lines, human breast cancer cell lines (MDA-MB-231 and MCF-7) as well as human melanoma cells (A-375 and 518A2). It was found that the synthesized compounds induce apoptosis in high concentrations (IC50 >30 μM) nonetheless, the observed morphological changes of studied cell lines during cell viability assay prompted us to examine their antimetastatic properties. Novel compound MBDR-4 significantly reduces migration and invasiveness of the MDA-MB-231 and A375 cancer cell lines at subapoptotic concentration (5 μM), which open new avenues for redirecting drug development of selective HDAC6 inhibitors as adjuvant chemotherapeutics, with antimetastatic effects.
AB  - Истраживачи тренутно улажу велике напоре у испитивање селективних
инхибитора хистон деацетилазе 6 (HDAC6i) 1,2 који би могли да нађу клиничку
примену 3 . Ова истраживања су делимично отежана услед неконзистентних
преклиничких резултата о ћелијским и биохемијским променама након
третмана солидних тумора HDAC6i(4,5). Наша студија обухвата компјутерски дизајн и синтезу три нова HDAC6
инхибитора, заједно са in vitro ензимским испитивањем активности на
сродним изоформама HDAC ензимима. Антинеопластичан ефекат синтетисаних једињења је испитан in vitro на четири типа ћелија карцинома,
хуманим ћелијама карцинома дојке (MDA-MB-231 и MCF-7) и хуманим ћелијама меланома (A-375 и 518A2). Утврђено је да синтетисана једињења
индукују апоптозу при високим концентрацијама (IC 50 >30 μM). Истовремено је уочено да ова једињења доводе и до морфолошких промена на третираним ћелијама током извођења теста виабилности што нас је усмерило ка испитивању њихових антиметастатских особина. Једињење MBDR-4
снажно инхибира миграцију и инвазивност MDA-MB-231 и A375 ћелија канцера на субапоптотској концентрацији (5 μM), што отвара нове могућности
за истраживање селективних HDAC6 инхибитора као адјувантних хемотерапеутика са антиметастатским ефектом.
PB  - Serbian Medical Society Oncology Section
C3  - 56th Cancerology week, Hotel Crowne plaza, November, 6 - 9. 2019, Belgrade, Serbia
T1  - Is there a borderline between cytotoxic and antimetastatic effects of selective Histone deacetylase 6 inhibitors in solid malignancies?
T1  - Постоји ли граница између цитотоксичног и
антиметастатског ефекта селективних инхибитора
хистон деацетилазе 6 код солидних тумора?
SP  - 264
EP  - 266
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4928
ER  - 

@conference{
author = "Nikolić, Katarina and Ružić, Dušan and Beljkaš, Milan and Petković, Miloš and Gul, Sheraz and Santibanez, Juan and Srdić Rajić, Tatjana",
year = "2019",
abstract = "Academia and industry make an extensive effort to discover selective histone deacetylase 6 inhibitors (HDAC6i) which could be delivered to the patients. These attempts are partially obscured by inconsistency in preclinical data regarding the cellular and biochemical changes upon treatment of solid tumours with HDAC6i. In this study, we present computational design, synthesis of three novel HDAC6 inhibitors along with their in vitro pharmacological profile against zinc-dependent HDACs. The in vitro anticancer effects of the synthesized compounds were examined on four types of cancer cell lines, human breast cancer cell lines (MDA-MB-231 and MCF-7) as well as human melanoma cells (A-375 and 518A2). It was found that the synthesized compounds induce apoptosis in high concentrations (IC50 >30 μM) nonetheless, the observed morphological changes of studied cell lines during cell viability assay prompted us to examine their antimetastatic properties. Novel compound MBDR-4 significantly reduces migration and invasiveness of the MDA-MB-231 and A375 cancer cell lines at subapoptotic concentration (5 μM), which open new avenues for redirecting drug development of selective HDAC6 inhibitors as adjuvant chemotherapeutics, with antimetastatic effects., Истраживачи тренутно улажу велике напоре у испитивање селективних
инхибитора хистон деацетилазе 6 (HDAC6i) 1,2 који би могли да нађу клиничку
примену 3 . Ова истраживања су делимично отежана услед неконзистентних
преклиничких резултата о ћелијским и биохемијским променама након
третмана солидних тумора HDAC6i(4,5). Наша студија обухвата компјутерски дизајн и синтезу три нова HDAC6
инхибитора, заједно са in vitro ензимским испитивањем активности на
сродним изоформама HDAC ензимима. Антинеопластичан ефекат синтетисаних једињења је испитан in vitro на четири типа ћелија карцинома,
хуманим ћелијама карцинома дојке (MDA-MB-231 и MCF-7) и хуманим ћелијама меланома (A-375 и 518A2). Утврђено је да синтетисана једињења
индукују апоптозу при високим концентрацијама (IC 50 >30 μM). Истовремено је уочено да ова једињења доводе и до морфолошких промена на третираним ћелијама током извођења теста виабилности што нас је усмерило ка испитивању њихових антиметастатских особина. Једињење MBDR-4
снажно инхибира миграцију и инвазивност MDA-MB-231 и A375 ћелија канцера на субапоптотској концентрацији (5 μM), што отвара нове могућности
за истраживање селективних HDAC6 инхибитора као адјувантних хемотерапеутика са антиметастатским ефектом.",
publisher = "Serbian Medical Society Oncology Section",
journal = "56th Cancerology week, Hotel Crowne plaza, November, 6 - 9. 2019, Belgrade, Serbia",
title = "Is there a borderline between cytotoxic and antimetastatic effects of selective Histone deacetylase 6 inhibitors in solid malignancies?, Постоји ли граница између цитотоксичног и
антиметастатског ефекта селективних инхибитора
хистон деацетилазе 6 код солидних тумора?",
pages = "264-266",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4928"
}

Nikolić, K., Ružić, D., Beljkaš, M., Petković, M., Gul, S., Santibanez, J.,& Srdić Rajić, T.. (2019). Is there a borderline between cytotoxic and antimetastatic effects of selective Histone deacetylase 6 inhibitors in solid malignancies?. in 56th Cancerology week, Hotel Crowne plaza, November, 6 - 9. 2019, Belgrade, Serbia
Serbian Medical Society Oncology Section., 264-266.
https://hdl.handle.net/21.15107/rcub_farfar_4928

Nikolić K, Ružić D, Beljkaš M, Petković M, Gul S, Santibanez J, Srdić Rajić T. Is there a borderline between cytotoxic and antimetastatic effects of selective Histone deacetylase 6 inhibitors in solid malignancies?. in 56th Cancerology week, Hotel Crowne plaza, November, 6 - 9. 2019, Belgrade, Serbia. 2019;:264-266.
https://hdl.handle.net/21.15107/rcub_farfar_4928 .

Nikolić, Katarina, Ružić, Dušan, Beljkaš, Milan, Petković, Miloš, Gul, Sheraz, Santibanez, Juan, Srdić Rajić, Tatjana, "Is there a borderline between cytotoxic and antimetastatic effects of selective Histone deacetylase 6 inhibitors in solid malignancies?" in 56th Cancerology week, Hotel Crowne plaza, November, 6 - 9. 2019, Belgrade, Serbia (2019):264-266,
https://hdl.handle.net/21.15107/rcub_farfar_4928 .