TY  - CONF
AU  - Ružić, Dušan
AU  - Đoković, Nemanja
AU  - Santibanez, Juan
AU  - Pavić, Aleksandar
AU  - Ganesan, A.
AU  - Srdić- Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://www.sdir.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2096
AB  - Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that has poor survival rates due to the
absence of specifi c 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 posttransla
tional modifi cations 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-specifi c targeting of HDACs is considered
a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, nonselec
tive 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 diff erent hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with
nanomolar IC50 values and two non-selective HDAC inhibitors were identifi ed. 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 zebrafi sh MDA-MB-231 xenograft model demonstrated that a novel
non-selective HDAC inhibitor (compound 8b) with a seven-carbon-atom linker exhibited potent eff ects against tumor
growth, metastasis, and angiogenesis at low micromolar concentrations.
PB  - Belgrade :  Serbian Association on for Cancer Research
C3  - 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR)
T1  - Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study
EP  - 26
IS  - 1
SP  - 26
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2096
ER  - 

@conference{
author = "Ružić, Dušan 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 specifi c 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 posttransla
tional modifi cations 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-specifi c targeting of HDACs is considered
a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, nonselec
tive 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 diff erent hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with
nanomolar IC50 values and two non-selective HDAC inhibitors were identifi ed. 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 zebrafi sh MDA-MB-231 xenograft model demonstrated that a novel
non-selective HDAC inhibitor (compound 8b) with a seven-carbon-atom linker exhibited potent eff ects against tumor
growth, metastasis, and angiogenesis at low micromolar concentrations.",
publisher = "Belgrade :  Serbian Association on for Cancer Research",
journal = "6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR)",
title = "Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study",
pages = "26-26",
number = "1",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2096"
}

Ružić, D., 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 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR)
Belgrade :  Serbian Association on for Cancer Research.(1), 26-26.
https://hdl.handle.net/21.15107/rcub_imagine_2096

Ružić D, 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 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR). 2023;(1):26-26.
https://hdl.handle.net/21.15107/rcub_imagine_2096 .

Ružić, Dušan, 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 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR), no. 1 (2023):26-26,
https://hdl.handle.net/21.15107/rcub_imagine_2096 .