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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
5-naphthylidene-2,4-thiazolidinediones:
In silico
studies, synthesis and primary cytotoxicity evaluation in
leukemic cell lines
Neha Upadhyay
1
, Kalpana Tilekar
1
, Piotr Mrowka
2
, Pramodkumar Gupta
3
, Virupaksha A Bastikar
4
, Kaustubh Wagle
1
and
C S Ramaa
1
1
Bharati Vidyapeeth’s College of Pharmacy, India
2
Medical University of Warsaw, Poland
3
D Y Patil University, India
4
Amity University, India
Introduction:
Contribution of antidiabetic Thiazolidinediones (TZDs) to cancer therapy has been evidenced by numerous
in-vitro
and
in-vivo
studies. While TZDs are known to stimulate PPAR-γ receptor, they also have multiple PPARγ independent
effects and the specific role of PPARγ activation in the anticancer effects of TZDs is still under investigation. Also, several
reports show the correlation between full activation of PPARγ and associated adverse effects. This prompted us to develop TZD
analogues as partial PPARγ agonists and evaluate their anticancer potential.
Methods:
We designed series of novel TZDs based on, QSAR model, Docking analysis and Molecular properties study. Further
we synthesized and structurally characterized them by 1H-NMR,
13
C-NMR, FTIR and Mass spectroscopy.
Results & Discussion:
In the present work, a QSAR model was developed and validated using 25 TZD derivatives synthesized
in our laboratory earlier, showing antiproliferative activity against K 562 cell lines, by using experimental and computational
study and analysis. The predicted activities by our QSAR models were very close to those experimentally observed, indicating
that these models can be safely applied for prediction of more effective hits having the same skeletal framework. We used this
model to design new series of 5-naphthylidene-2,4- TZDs and predicted their antiproliferative activity. The molecules from
the series, obeying Lipinski’s rule of five were subjected to docking analysis using VLife protocol. The molecules displaying
desired interactions as that of partial agonists of PPARγ were further taken for synthesis and evaluated for primary cytotoxic
effects on several cancerous cell lines.
Biography
Neha Upadhyay has completed her Post-graduation in Pharmaceutical Chemistry from Bombay College of Pharmacy, Mumbai. She is working as a Junior
Research Fellow (JRF) on a project funded by DST, India. She has registered for PhD in Pharmaceutical Sciences at Bharati Vidyapeeth’s College of Pharmacy,
Navi Mumbai, India.
upadhyayneha16@gmail.comNeha Upadhyay et al., Med chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-039