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Journal of Pharmacology and Therapeutic Research
Volume 1 Issue 1
Clinical Pharmacy 2017
Notes:
Page 35
December 07-09, 2017 | Rome, Italy
7
th
World Congress on
Clinical Pharmacy and Pharmacy Practice
In searching of the magic bullet: The role of
heme oxygenase-1 in cancer
Valeria Pittalà
University of Catania, Italy
H
eme Oxygenases (HO) are family of microsomial
enzymes that catalyze heme regiospecific catabolism.
HO-1 overexpression is detected in many cancers and its
selective inhibition is acknowledged as a new therapeutic
opportunity. The first generation of HO-1 inhibitors were
soon discontinued due to their pharmacological profile. In
the search of HO-1 inhibitors with novel chemical structure,
proprietary azole-based compounds were reconsidered
as HO-1 inhibitors. Basing on virtual screening results, we
tested a compound library possessing two key-features:
a N-3 imidazole nitrogen able to coordinate heme ferrous
iron and a hydrophobic moiety (Fig. 1). Biological assays
revealed high inhibitory activity towards HO-1 and, for
some derivatives towards HO-2. Chemical optimization of
azole-based derivatives was performed, and most potent
compounds were studied for their antitumor properties in
different cancer cell lines (imatinib-resistant LAMA-84 R,
DU-145, PC3, LnCap, MDA-MB-231, and MCF-7) with
highly promising results. Some compounds were able to
restore imatinib sensitivity in LAMA-84 R cells. Preliminary
results of in vivo studies will be presented. Moreover,
new potent and specific ligands for HO-1 and/or HO-2
have been identified. Formulation strategies including
nanoparticles have been used to improve pharmacological
profile of some selected derivatives and will be the object
of the present talk. Finally, elucidation of HO-1 inhibition
role in tumor will guarantee useful therapeutic applications
in cancer therapy.
Biography
Valeria Pittalà has completed her MSc in CTF, PhD in Pharmaceutical Sciences
at the University of Catania (Italy), and joined Pharmacia Corporation. There
she has worked as Member of Combinatorial Chemistry Group, contributed
to the discovery of Danusertib, currently under clinical investigation, being
Co-Inventor of Bicyclopyrazoles class. Subsequently, she has returned to the
University of Catania as Medicinal Chemistry Professor. She is highly motivated
drug discovery Scientist and project Leader with proven leadership capability,
interpersonal skill, and independence in achieving given objectives. She has
published over 60 patents and peer-reviewed papers in reputed journals and
has been serving as an Editorial Board Member of repute.
vpittala@unict.itValeria Pittalà, J Pharmacol Ther Res 2017