TY  - JOUR
AU  - Ruzic, Dusan
AU  - Ellinger, Bernhard
AU  - Djokovic, Nemanja
AU  - Santibanez, Juan F.
AU  - Gul, Sheraz
AU  - Beljkas, Milan
AU  - Djuric, Ana
AU  - Ganesan, Arasu
AU  - Pavić, Aleksandar
AU  - Srdic-Rajic, Tatjana
AU  - Petkovic, Milos
AU  - Nikolic, Katarina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1662
AB  - Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.
T2  - Pharmaceutics
T2  - Pharmaceutics
T1  - Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation
IS  - 12
SP  - 2600
VL  - 14
DO  - 10.3390/pharmaceutics14122600
ER  - 

@article{
author = "Ruzic, Dusan and Ellinger, Bernhard and Djokovic, Nemanja and Santibanez, Juan F. and Gul, Sheraz and Beljkas, Milan and Djuric, Ana and Ganesan, Arasu and Pavić, Aleksandar and Srdic-Rajic, Tatjana and Petkovic, Milos and Nikolic, Katarina",
year = "2022",
abstract = "Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.",
journal = "Pharmaceutics, Pharmaceutics",
title = "Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation",
number = "12",
pages = "2600",
volume = "14",
doi = "10.3390/pharmaceutics14122600"
}

Ruzic, D., Ellinger, B., Djokovic, N., Santibanez, J. F., Gul, S., Beljkas, M., Djuric, A., Ganesan, A., Pavić, A., Srdic-Rajic, T., Petkovic, M.,& Nikolic, K.. (2022). Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation. in Pharmaceutics, 14(12), 2600.
https://doi.org/10.3390/pharmaceutics14122600

Ruzic D, Ellinger B, Djokovic N, Santibanez JF, Gul S, Beljkas M, Djuric A, Ganesan A, Pavić A, Srdic-Rajic T, Petkovic M, Nikolic K. Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation. in Pharmaceutics. 2022;14(12):2600.
doi:10.3390/pharmaceutics14122600 .

Ruzic, Dusan, Ellinger, Bernhard, Djokovic, Nemanja, Santibanez, Juan F., Gul, Sheraz, Beljkas, Milan, Djuric, Ana, Ganesan, Arasu, Pavić, Aleksandar, Srdic-Rajic, Tatjana, Petkovic, Milos, Nikolic, Katarina, "Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation" in Pharmaceutics, 14, no. 12 (2022):2600,
https://doi.org/10.3390/pharmaceutics14122600 . .