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alliedacademies
Asian Journal of Biomedical and Pharmaceutical Sciences | Volume 8
May 14-15, 2018 | Montreal, Canada
Global Summit on
Biopharma & Biotherapeutics
Cancer is the second leading cause of death globally and
was responsible for 8.8 million deaths in 2015. The
development of novel molecules and targeted therapies
has gained attention because of currently available
chemotherapeutic methods of limitations such as side
effects/toxicity of existing drugs, high metastatic rates, and
drug resistance. The improvement of the design of metal-
based therapeutic agents which have a very important
role in cancer treatment, have been accelerated by the
development of platinum complexes. In the treatment
of anticancer properties of metal complexes, many
studies have been carried out on the development of new
compounds with less toxic effect. Ruthenium is thought
to have a lower side-effect profile, especially in platinum-
resistant cancers and all other cancers, due to the greater
accumulation of ruthenium, especially in cancer cells
and hypoxic environments as well. Studies of anticancer
and antimetastatic properties of ruthenium complexes
have been published. Ruthenium complexes have been
shown to be effective compounds in many cancers such as
melanoma, lymphoma, breast and gastrointestinal cancers.
It has been emphasized in many research articles that
ruthenium complexes of phenanthroline-like compounds’
toxicity are lower and show higher cytotoxic and apoptotic
activity as compared with cisplatin. In cancer, activation
of tyrosine kinases and intracellular pathway increases
proliferation and angiogenesis and prevents apoptosis.
Sorafenib is a multikinase inhibitor that has been approved
for renal cell carcinoma, hepatocellular carcinoma, thyroid
cancer, and the study of Sorafenib continues in other types
of cancers. Sorafenib, which inhibits tumor proliferation
and angiogenesis, in addition to Raf kinase also inhibits
receptor tyrosine kinases such as VEGFR, PDGFRβ, c-KIT,
RET. Receptor tyrosine kinases play a role in many cellular
events such as proliferation and differentiation, cell survival
and metabolism, cell cycle control. The fact studies that
obtaining new metal complexes of the known drug active
substances and investigation of their activities enable to
reach the new drug substance in a shorter time and a lower
cost has led to a remarkable increase in the researches in
this field. Based on this data, in this study, firstly Sorafenib
and ruthenium complexes of Sorafenib bearing hetrocyclic
structures prepared as regards to valuable literature data.
The structures of the obtained compounds were elucidated
by elemental analysis, NMR, UV-Vis, FT-IR and APCI-LC/MS
methods. Biological activity studies of the obtained products
are performed. In this part of the study, MTT assay, cell cycle
assay, apoptosis/cell death assay, in vitro tyrosine kinase
assay, Western blot assay will be conducted. In addition,
copolymers of poly (ethylene glycol) methyl ether-block-poly
(D, L-lactate) (PEG-b-PLA) obtained to prepare polymeric
micelles with active Sorafenib/metal complexes and drug
release profiles examined. Finally, molecular modeling
studies conducted by utilizing project outputs
e:
Synthesis of new sorafenib/ruthenium complexes and development of polymeric carrier systems to
investigate drug potentials
Kadriye Benkli
Bezmialem University, Turkey