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.com
Volume 8
Medicinal Chemistry
ISSN: 2161-0444
Medicinal Chemistry 2018
June 14-15, 2018
June 14-15, 2018 | Barcelona, Spain
10
th
World Congress on
Medicinal Chemistry and Drug Design
Targeting epigenetics: Synthesis and biological evaluation of difluorinated propanediones as HMTase
inhibitors
Kalpana Tilekar
1
, Neha Upadhyay
1
, Tanushree Pal
1
, Sanjay Gupta
2
and
C S Ramaa
1
1
Bharati Vidyapeeth’s College of Pharmacy, India
2
Tata Memorial Centre-ACTREC, India
Introduction:
Pharmaco-epigenomics constitute the hope for a new strategy in cancer treatment owing to epigenetic
deregulation, a reversible process, suspected of playing a role in malignancy 30 years prior to the sequencing of the human
genome. In this field, several enzymes like HDACs, DNA methyl transferases (DNMTs) and histone methyl transferases
(HMTase) have been studied extensively for their capability to be inherited by natural or synthetic compounds. To date, HDAC
and DNMT inhibitors are used in cancer therapy are tested in clinical studies. In contrast to this, the search for inhibitors of
HMTase is still in its infancy and
in-vivo
data of most of the agents are not available.
Methods:
In this research work, we synthesized few difluorinated propanediones and their structures were determined by
analytical and spectral (FTIR, 1H NMR,
13
C NMR) methods. The newly synthesized compounds were first evaluated for their
antiproliferative activity and then for HTMase inhibitory potential in leukemic cell lines. We have also performed cell cycle
analysis to study cell growth arrest.
Results:
Amongst all the synthesized compounds, PR-4 was found to be most active. In the cytotoxicity assay, it showed cell
growth of 42.6 % and 53.4% comparable to that of adriamycin; 44.5% and 53.2% in U937 and JURKAT, respectively. At a
concentration of 1 and 10μM, it had shown to alter the methylation levels in two leukemic cell lines of histiocytic lymphoma
(U937) and acute T-cell leukemia (JURKAT). Cell growth arrest was found in the G0/G1 phase in both the cell lines.
Discussion:
The apoptosis pattern suggests that the molecule PR-4 could emerge as a potential anticancer agent by targeting
HMTases.
Biography
Kalpana Tilekar has completed her Post-graduation in Pharmaceutical Chemistry, from Bharati Vidyapeeth’s College of Pharmacy, Mumbai. She worked as an
Assistant Professor at NCRD’s Sterling Institute of Pharmacy, Navi Mumbai, India. Currently, she is working as Junior Research Fellow (JRF) on a project funded
by DST, India and she is registered for PhD in Pharmaceutical Sciences at Bharati Vidyapeeth’s College of Pharmacy, Navi Mumbai, India.
kalpana.tilekar@gmail.comKalpana Tilekar et al., Med chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-039