medicinal-chemistry-2018-posters-abstracts

3 / 29

Page 64
Notes:
conferenceseries.com
Volume 8 Medicinal Chemistry
ISSN: 2161-0444 Medicinal Chemistry 2018
June 14-15, 2018
June 14-15, 2018 | Barcelona, Spain
10th World Congress on
Medicinal Chemistry and Drug Design
Fluorinated anti-tubulin phenyl-pyrroloquinolinones: In vitro and in vivo anticancer properties
Matteo Dal Prà
University of Padua, Italy
Tricycle Phenyl-Pyrroloquinolinones (PPyQs) are a class of compounds that have showed interesting in vitro and in vivo
anti-proliferative activity acting as tubulin polymerization inhibitors by binding at the colchicine site into β-tubulin.
The major initial focus on introducing fluorine into biologically active compounds is to improve their metabolic stability
by blocking potential reactive positions with fluorine. In an attempt to reduce the oxidative metabolism of 7-PPyQs and at
the same time to possibly maintain the excellent pharmacodynamic, we designed the synthesis of some compounds 12-15
and 19, monofluoro-phenyl derivatives of the earlier 3-ethyl-7-PPyQ 20 and 3-benzoyl-7-PPyQ 21. Of the new compounds
synthesized, potent cytotoxicity (low and sub-nanomolar GI50 values) was observed with 12 and 13, both more potent than
20, in both leukemic and solid tumor cell lines. Neither compound 12 nor 13 induced significant cell death in normal human
lymphocytes, suggesting that the compounds may be selectively active against cancer cells. In particular, 13 was a potent inducer
of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation
of the mitochondrial transmembrane potential and production of reactive oxygen species, indicating that cells followed the
intrinsic pathway of apoptosis. Experiments carried out in a mouse syngeneic model demonstrated high antitumor activity of
13, which significantly reduced the tumor mass at doses four-ten times lower than that required for the CA-4P used as reference
compound. Finally, molecular docking and metabolic stability studies of the newly synthesized compounds will be reported.
Biography
Matteo Dal Prà has completed his PhD at the University of Padova, School of Medicine, Department of Pharmaceutical and Pharmacological Sciences.
Matteo Dal Prà, Med chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-040