@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"
}